Ethical considerations of genetic and genomic testing in pediatric oncology: A narrative review.

INTRODUCTION
Over the past few decades, advances in genomic testing have transformed oncology, driving a shift toward precision medicine. Innovations in testing methods, development of targeted agents, and broader access to testing have changed clinical oncology practice.
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Genomic testing in pediatric oncology presents considerations unique from this testing in adult oncology. Compared with adults, there are fewer data regarding test performance, variant interpretation, and the clinical utility of genomically informed interventions for children and adolescents.
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Nevertheless, genomic findings in pediatric patients may have implications beyond the individual patient, affecting parents, siblings, and other relatives and raising questions around consent, assent, privacy, and psychosocial impact. As the use of genomic testing expands in pediatric oncology, careful attention to its integration in clinical care—and to its effects on patients and family—is essential. This narrative review explores these evolving dimensions.

CANCER GENOMICS TERMINOLOGY
Genetic and genomic testing are now a routine part of oncology, providing information that can refine diagnosis, guide therapy, and inform familial risk. Understanding the distinctions between testing types, their scopes, and their implications is essential for clinicians and families navigating these results.

Genetic testing generally refers to targeted analysis of one or a few genes, selected based on clinical suspicion—for example, testing TP53 in a child with adrenocortical carcinoma or DICER1 in a patient with a cystic lung lesion.
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Genomic testing encompasses broader sequencing approaches, such as multigene panels, whole‐exome sequencing, or whole‐genome sequencing, potentially capturing both known and novel variants.
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Sometimes, these genomic testing modalities are referenced more generally as next‐generation sequencing.
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These assays typically sequence DNA, although RNA‐based approaches may be used to identify expressed variants or gene fusions.

Germline testing assesses inherited or sporadic variants from nontumor tissue, such as blood, saliva, or skin fibroblasts (or, sometimes, inherited or sporadic variants expressed in the tumor tissue itself).
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Targeted germline genetic testing typically focuses on established cancer‐predisposition genes, whereas germline genomic testing can reveal both known and novel risk alleles. Germline findings can guide surveillance strategies, inform treatment decisions, and may have implications for family members through cascade testing.

Tumor testing evaluates DNA or RNA from cancer tissue to identify tumor (somatic) alterations that drive tumor behavior or inform therapy.
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For instance, detection of an NTRK fusion in infantile fibrosarcoma confirms diagnosis and identifies a targeted therapeutic option.
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Genetic alterations in a tumor can be specific to the tumor or to the person themselves. Broader tumor genomic profiling may uncover actionable variants but may also reveal information about the germline because the tumor will harbor any variants that exist in the germline. To determine whether it is a true germline or somatic variant, confirmatory testing is needed. This may be performed through targeted testing of that variant in the germline or through a process of paired tumor‐normal testing.
Each testing modality—genetic or genomic—can be applied to either tumor or germline samples. For example, genetic testing may be performed on a tumor specimen, such as testing for ALK rearrangement on a lymph node biopsy in a patient with lymphoma, or on a germline specimen, such as blood testing for WT1 in a patient with Wilms tumor.
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Similarly, genomic testing may be performed on a tumor specimen, such as sequencing a sarcoma biopsy with a large cancer gene panel, or on a germline specimen, such as performing whole‐exome sequencing on skin fibroblasts from a patient with acute myeloid leukemia. Across these approaches, careful use of precise and consistent language is essential.
Clear terminology is particularly important when describing variant classification—the assessment of the clinical significance of a genetic alteration. Variants are typically categorized as pathogenic, likely pathogenic, likely benign, benign, or variants of uncertain significance (VUS), the latter referring to changes for which clinical significance is not yet established in a particular disease/setting.
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Uncertainty may arise at both the variant level (VUS) and, particularly in research or expanded panel testing, at the gene–disease level, in which the clinical relevance of a given gene remains unclear. Genomic testing may also yield secondary findings, which are variants intentionally analyzed but unrelated to the primary testing indication, or incidental findings, which are unexpected variants detected during analysis and that are likewise unrelated to the primary testing indication.
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Throughout this review, we use the more general term genomic to refer collectively to both genetic (targeted) and genomic (broad) testing, unless a specific distinction is needed. Table 1 summarizes key testing modalities, their scope, sample sources, clinical purposes, and potential implications; and Figure 1 demonstrates a conceptual overview of genetic and genomic testing in pediatric oncology. This provides a foundation for understanding how genomic information informs modern pediatric oncology care, setting the stage for a discussion of its impact on diagnosis, therapy, and long‐term patient outcomes.

ROLE OF GENOMICS IN PEDIATRIC ONCOLOGY
Survival rates in childhood cancer have dramatically improved over prior decades, with 5‐year survival increasing from roughly 10% in the early 1960s, to just over 60% in the mid‐1970s, to 85% in recent years.
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Yet, whereas childhood cancer is relatively rare compared with adult cancer, it remains the leading cause of disease‐related death in children after infancy.
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These trends underscore the need for approaches that are both more precise and more individualized—a role increasingly filled by genomic testing.
Genomic testing has become an increasingly integral component of caring for children and adolescents with cancer.
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Early approaches focused on cytogenetic analysis and single‐gene testing of tumor specimens (genetic testing), but advances in sequencing technology now allow for tumor testing using multigene panels, whole‐genome sequencing, whole‐exome sequencing, RNA sequencing, and many other advanced genomic testing modalities (collectively referred to as genomic testing).
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Testing may be conducted as part of standard clinical care of a patient or as a component of research protocols.
Genomic testing of tumors serves multiple purposes. It can clarify diagnosis, such as identifying an EWSR1 rearrangement to confirm a diagnosis of Ewing sarcoma, or inform risk stratification, such as detection of ETV6‐RUNX1, a gene fusion that portends favorable prognosis in pediatric B‐cell acute lymphoblastic leukemia.
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In some cases, tumor genomic results may guide therapy, for example, the addition of a tyrosine kinase inhibitor to treat B‐cell acute lymphoblastic leukemia carrying a BCR‐ABL fusion or the use of a BRAF inhibitor in Langerhans cell histiocytosis harboring BRAF V600E.
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Upfront paired tumor‐normal specimens for sequencing at the same time on the same platform may enhance the identification of somatic alterations and, in the research context, may provide novel insights on tumor biology and germline contribution to cancer.
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In addition, germline testing may reveal hereditary cancer syndromes, creating opportunities for cascade testing in parents and siblings and facilitating cancer screening for those who have an increased risk of cancer and for whom such screening is anticipated to prove beneficial.
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Despite its promise, pediatric genomic testing in oncology presents various challenges. Interpretation of genomic results can be complex, particularly for VUS, and because of the small numbers of pediatric patients that limit available data for many tumor types. Translational gaps remain because many targeted therapies have only been studied in adults, in whom tumor biology may differ.
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There are also limitations in informed consent processes—particularly because of potential secondary findings on tumor genomic testing, especially with upfront, paired tumor‐normal genomic sequencing. Although genomic testing has the potential to transform care, its benefits are contingent on equitable access, accurate interpretation, and thoughtful integration into patient‐centered and family‐centered clinical workflows—issues we explore further below.

ACCESS CONSIDERATIONS

Access to testing
Costs, financial coverage, and insurance reimbursement for genetic testing in oncology have improved over prior decades, but these remain challenging issues. The estimated cost for sequencing a genome has dropped drastically; the Human Genome Project was estimated to have cost upward of $1 billion, whereas recent sequencing efforts typically cost under $1000 per genome.
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Advances in financial coverage and insurance reimbursement, however, have been slower.
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Some patients with cancer are faced with deciding whether to finance testing out‐of‐pocket, meet out‐of‐pocket expenses required by their insurer, or not pursue testing. Given these burdens, a 2024 study indicated that most oncologists surveyed rated patient insurance and out‐of‐pocket costs for genomic tests as important considerations in their subsequent treatment recommendations.
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Disparities in access to testing are amplified among patients with lower socioeconomic status, those who are underinsured or uninsured, and those who identify as a member of a minoritized race or ethnicity.
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Although this review focuses on the United States, access to genomic testing also differs considerably across countries and regions, reflecting variation in health care infrastructure, national resource allocation, and regulatory environments.
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Even within high‐resource settings, access to testing and specialized expertise is not equally distributed across institutions, with availability often more limited in rural settings or community‐based practices compared with large academic centers.
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These gaps in access to comprehensive data may further widen disparate outcomes in treatment for minoritized or disadvantaged groups.
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These challenges are often amplified in the pediatric population, in which a distinction must be drawn between routine somatic testing and comprehensive genomic profiling. The clinical utility of more comprehensive testing, like cancer gene panels—as opposed to routine diagnostic testing, like FOXO1 fusion in rhabdomyosarcoma—has not yet been fully established. Although published recommendations exist for both somatic and germline testing in select clinical scenarios,
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such criteria may be inconsistently applied in practice, particularly when the testing moves beyond the minimum requirements for initial risk stratification. This creates an ethical tension in which access to potentially clinically meaningful precision therapies may depend more on a family's zip code or insurance plan than on the biologic characteristics of the child's tumor.
Still, access to various types of genomic sequencing for some pediatric patients may be available without the need for insurance coverage or out‐of‐pocket costs through coverage by philanthropic or institutional funds—which can both contribute to and mitigate disparate access, depending on the particular circumstance, as examined below. This testing may also occur through enrollment in research protocols. In 2022, the Molecular Characterization Initiative (MCI) was launched, which is the result of a collaboration between the National Cancer Institute and Children's Oncology Group (COG).
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In this program, children, adolescents, and young adults with specified solid tumors who receive treatment at hospitals affiliated with COG are eligible to enroll on a tissue banking protocol through which they are able to undergo somatic and germline sequencing. In the first year of the MCI, results were returned to more than 1000 participants and their oncologists. As of May 2025, almost 7000 patients have undergone testing through this mechanism.
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In addition, many children with cancer receive upfront treatment on a clinical trial, with some of these trials also offering sequencing relevant to the cancer type without additional cost to the patient/family.
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In addition to these national collaborative trials, some institutions or multi‐institutional groups have offered upfront genomic sequencing through research protocols, some including whole‐exome or whole‐genome sequencing and/or with the support of institutional or philanthropic funding.
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Although genomic sequencing obtained through a research protocol may mitigate the direct burden of the costs to the individual patient or institution, it raises two primary concerns. First, there are differential rates of research participation across pediatric patient group, such as minoritized individuals, adolescents and young adults, and patients whose primary language is one other than English, all of whom have lower rates of enrollment on research studies.
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In addition, coverage of such tests for free through the research study may be construed as unduly influential, exerting indirect pressure on a family to enroll on a clinical trial, even if they otherwise would prefer not to do so.
Another challenge associated with pursuing genomic sequencing through a research protocol is the difficulty with obtaining quality informed consent to research participation around the time of a new cancer diagnosis. This has long been acknowledged as a challenge in pediatric oncology—in both clinical care and research settings.
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A patient and their parents are tasked with receiving information in the context of a distressing situation, which must be understood and promptly integrated into decision‐making. This is likely even more difficult when a research protocol includes germline testing paired with the somatic testing, like the MCI, which has the potential to identify cancer‐predisposition syndromes in the patient—and potentially in the patients' family members.
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This challenge of identifying cancer predispositions is not unique to research testing or to paired tumor‐normal testing. Even clinical tumor‐only genomic sequencing can identify a potential germline variant but cannot determine whether the alteration is somatic or germline without confirmatory testing. This possibility underscores the need for adequate pretest consent, including high‐quality patient and family education.
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Achieving this can be difficult in the abbreviated and stressful timeframe surrounding a new cancer diagnosis, when clinicians face competing demands and limited time for in‐depth counseling.
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Some institutions have adopted a staged consent approach to address these challenges, which has been shown to improve parents' knowledge of concepts relevant to genomic sequencing and accommodate preferences for flexible timing after diagnosis.
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Institutions may develop unique approaches tailored to local resources and patient populations, but establishing a consistent, standardized process within each program remains essential for ensuring equitable care.

Access and application of results
Although advances have occurred in patient access to genomic testing itself, there continue to be challenges downstream once test results become available. As highlighted above, there are clear disparities among groups in access to testing. However, even when testing is attainable for a patient, there are disparities (some potential/hypothetical and some already seen) in how results are interpreted and applied—an issue relevant in both pediatric and adult care. Norms—particularly regarding which genomic findings are pathogenic and likely pathogenic versus those that are normal or a VUS—have been established using data largely from White, European patients.
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Research campaigns, including the All of Us program through the National Institutes of Health, have moved the needle slightly toward improvement of the diversity of representation, but much more work is necessary in this area.
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The term VUS reflects uncertainty in clinical significance at the time of classification; with additional data in relevant populations, these variants may later be reclassified. Whereas all recognize that classification may evolve, there is ongoing debate about how often sequencing data should be re‐analyzed.
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The small number of pediatric patients with cancer makes the interpretation of genomic findings uniquely challenging. Even when variants are detected, their biologic significance and clinical actionability are often uncertain. Nonetheless, the catalog of tumor genomic alterations relevant to childhood cancers continues to expand, including, for example, the growing list of variants that inform risk stratification in pediatric acute myeloid leukemia.
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Emerging evidence also suggests that genes previously associated with adult‐onset cancer predisposition may contribute to pediatric malignancies.
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It is important to note that the presence of a genomic alteration does not guarantee therapeutic efficacy. For example, ALK‐mutated tumors exhibit variable responses to ALK inhibitors across lung cancer, anaplastic large cell lymphoma, inflammatory myoblastic tumors, and neuroblastoma.
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Cancer biology
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reflects complex, context‐dependent interactions rather than simple one‐to‐one genotype–phenotype relationships, and the rarity of pediatric cancers limits opportunities for rigorous trials to establish genotype‐specific responses.
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These scientific and clinical uncertainties pose significant challenges for clinicians attempting to translate genomic findings into actionable treatment plans for pediatric patients.
Beyond initial fellowship training, professional development and continuing medical education for practicing pediatric oncology clinicians have struggled to keep pace with genomic advances. Contemporary research demonstrates that pediatric oncologists agree that understanding tumor and germline genomic information is essential for their practice.
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Despite this, pediatric oncology clinicians express discomfort with testing and with the application of results.
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In one study, only a minority (35%) of pediatric oncologists surveyed were confident in interpreting, using, and discussing somatic genomic test results.
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This is not dissimilar from adult oncologists, whose confidence varies by testing platform, genomic training, and practice infrastructure.
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This discomfort is compounded by a shifting clinical landscape; whereas germline testing and the management of cancer‐predisposition syndromes were traditionally the purview of geneticists and genetic counselors (GCs), these responsibilities have increasingly transitioned to pediatric oncologists over the last decade. This shift places an added burden on oncologists to navigate complex hereditary implications and long‐term surveillance protocols, tasks for which many feel underprepared.
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Beyond the interpretation of test results themselves, added challenges lie in translating genomic findings into therapeutic strategies. What is more, it is likely that obtaining a sufficient level of knowledge and confidence regarding genomic testing and its application to care will only become more challenging as genomic advances continue, increasing only more drastically the amount of knowledge required of pediatric oncology trainees and practicing clinicians.
Genomic testing can identify targeted therapies that may guide precision medicine in pediatric oncology. However, many of these targeted therapies have been studied only in adults, resulting in uncertainty about both their safety and their efficacy in children. Because pediatric cancers are rare—and even rarer when subdivided by molecular subtype—conducting pediatric‐specific clinical trials poses significant financial and logistical barriers.
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Consequently, clinicians and patients' families may face uncertainty about whether findings from adult populations are applicable to pediatric patients, which complicates both treatment decisions and the process of obtaining insurance coverage for targeted therapies.
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Likewise, identifying a genomic target does not always equate to drug access. Availability may be restricted by high costs, lack of pediatric‐specific labeling, and the logistical hurdles of enrolling in distant clinical trials.
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These barriers introduce significant equity and psychosocial challenges because families with fewer resources or those living far from major medical hubs may face greater difficulty navigating the complex insurance appeals or compassionate use applications required to secure testing and treatment.
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Such challenges illustrate the nuanced considerations surrounding genomic testing in pediatric oncology and set the stage for a closer examination of communication and decision‐making about genomic testing.

COMMUNICATION AND DECISION‐MAKING ABOUT GENOMIC TESTING
A substantial body of literature examines communication and decision‐making about genomic testing within the field of genetic counseling, and communication science in pediatric oncology has likewise advanced considerably over the past 2 decades.
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Whereas each field provides valuable insights applicable to genomic testing in pediatric oncology, research that directly addresses communication in this specific context remains limited. Effective integration of genomic testing into pediatric oncology requires thoughtful, developmentally tailored communication strategies by pediatric oncology clinicians across the care continuum (Figure 2). Although clear delineation of professional roles is important, the composition of multidisciplinary pediatric oncology teams may vary across institutions. We therefore use the term pediatric oncology clinicians, or clinicians, to broadly encompass the range of professionals involved in these discussions, recognizing that there will be variability from one institution to the next.

Pretest communication
Communication about genomic testing often occurs during emotionally overwhelming periods, such as at diagnosis or relapse, which can affect patients’ and families’ ability to process information.
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Families may have difficulty understanding the type and scope of testing being performed.
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Additional complexity may arise from the blurred boundaries between clinical and research‐based testing.
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Genomic testing offered in a research study may use clinically validated methods but serve different research aims, and expectations around the return of results can vary depending on study design. For example, a clinical trial may include genomic sequencing of a tumor for the purpose of determining eligibility to receive a targeted agent (e.g., identification of FLT3‐ITD in acute myeloid leukemia to guide incorporation of an FLT3 inhibitor).
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In this case, the patient and the treating clinician receive the genetic test result, which is also entered into the medical record. The same patient may be eligible to enroll on a clinical trial with the aim of validating a long‐read sequencing platform, in which neither the patient nor the treating clinician receives any sequencing results. These complex factors can contribute to confusion for families about what testing is being done, why it is being done, and how results will be communicated.
A clear illustration of this complexity is found in the COG ANBL1531 protocol (ClinicalTrials.gov identifier NCT03121599) for children with newly diagnosed neuroblastoma. When the trial initially opened, tumor testing for ALK variants was returned to clinical sites linked only to a research identification rather than a patient‐specific clinical report.
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Even when somatic ALK variants prompted germline evaluation, those results remained linked to research identifications and were not Clinical Laboratory Improvement Amendments–compliant. Consequently, to obtain the documentation required for insurance coverage of long‐term surveillance or cascade testing for family members, patients were often required to undergo redundant formal germline testing through commercial platforms. Although this process has since been streamlined through the MCI—which provides Clinical Laboratory Improvement Amendments–compliant, patient‐named reports—the initial transition and lingering distinction between research‐linked and clinically actionable data added significant layers of confusion for families and clinicians alike.
These challenges for families are often exacerbated by the rapidly evolving nature of personalized care and the lack of standardized communication strategies among clinicians.
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Even when a clinician is clear about the type or purpose of testing, the use of nonstandard terminology can inadvertently reinforce parental misconceptions.
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Because advances in medical technology may offer hope about improved treatments or outcomes, families’ expectations may exceed the clinical reality of the findings.
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For example, it has been reported that parents and young adults in genomic sequencing studies overestimated the likelihood of identifying a targetable germline variant or incorrectly expected that this sequencing would fundamentally improve the likelihood of cure.
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This expectational gap highlights how clinician‐level challenges in interpreting and communicating nuance can directly contribute to a family's psychological burden.
Much of the genetic counseling literature on pretest communication focuses on supporting families in navigating the decision of whether to pursue testing. In pediatric oncology, however, some genomic tests are standard‐of‐care and may be perceived as nonoptional, whereas others are supplemental or discretionary.
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The urgency of testing can also vary: certain tests are time‐sensitive for guiding immediate treatment decisions, whereas others can be postponed, allowing for more extensive pretest discussion (e.g., germline testing to evaluate for a possible cancer‐predisposition syndrome).
Consequently, there are situations in pediatric oncology—both perceived and actual—in which families have little to no choice about whether testing occurs. For example, a child with a new diagnosis of acute leukemia will undergo a bone marrow evaluation with testing to identify any of several high‐risk or low‐risk genomic variants that may impact upfront treatment.
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This test may be treated like other, nongenomic diagnostics, the results of which have prognostic significance, such as a complete blood count to evaluate the presenting white blood cell count and blast percentage. In these cases, the clinician may simply inform the family that the test will be performed.
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Few data are available about the consent process for testing like this; however, as genomic testing becomes ever more prevalent and central to pediatric oncology practice, it is likely that such testing is becoming more normalized and considered more similar to other nongenomic tests (e.g., testing blood for electrolytes, performing a chest x‐ray, etc.), without a discrete consent process/discussion.
This movement away from what is sometimes referred to as genetic exceptionalism, either intentionally or unintentionally, likely results in families having less control over whether or not genomic testing is performed.
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This limited decisional latitude raises important ethical considerations for how informed consent and communication are approached, particularly in ensuring that families understand the purpose, scope, and implications of testing even when it is not optional or is not within the zone of parental discretion to decline.
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The zone of parental discretion refers to the ethical space in which parents may make suboptimal, but not harmful, medical decisions for their child; outside of this zone, refusals are viewed as posing sufficient risk of harm to justify clinician intervention.
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If the parent's refusal of testing is thought to be outside of this zone (and thus potentially considered to fall into the category of mistreatment or even neglect of the child), some clinicians might choose to involve the court/state to obligate testing over the parent's objection (although this practice is typically limited to refusals of treatment, rather than testing itself).
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In this context, shared decision‐making has a unique structure in pediatrics: unlike in adult care, autonomy is not absolute, and clinicians may sometimes need to pursue necessary testing despite parental objection to act in the child’s best interest.
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Recognizing these differences underscores the importance of pediatric‐specific frameworks for communication and decision‐making about genomic testing.
Several considerations unique to pediatrics warrant explicit attention in communication and decision‐making with regard to genomic testing (Table 2). First is how much to integrate a child into the decision‐making process—a consideration that is not relevant in adult genomic testing because the capacitated patient’s decision is paramount in such settings. How much of a role the child should play in this decision‐making varies, of course, on the age and developmental stage of the patient as well as clinical factors like prognosis and the implications of the testing.
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For instance, for a preference‐sensitive decision such as whether to send upfront germline sequencing alongside somatic tumor sequencing for a patient with a new solid tumor diagnosis, the child’s age can affect how much their preferences factor into a decision.
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A toddler would not be involved in any pretest discussion, whereas an adolescent patient’s preferences should be factored more significantly into the decision.
Another concept regarding genetic testing in pediatrics is the consideration of a child’s right to an open future.
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Historically, ethicists have argued against genetic testing for adult‐onset conditions before a child reaches the age of majority and is able to fully participate in the decision‐making and consent process related to genetic testing.
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However, this is less straightforward in a child who already has a diagnosis of cancer.
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Sending paired germline sequencing along with somatic sequencing may be beneficial to the interpretation of the somatic results. DNA‐based or RNA‐based cancer gene panels may include genes typically considered associated with adult‐onset cancers, such as BRCA1 or CHEK2.
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Whereas these may not be currently understood to be associated with the child’s active cancer diagnosis, they may affect screening for that child later in life.
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However, it also may be more pressingly relevant to adult relatives of the child. A child’s results on this panel may direct cascade testing in family members and, if present, may inform recommendations for cancer screening in those relatives. Therefore, thoughtful communication during pretest counseling is essential to set expectations for families—helping them understand both the potential implications for the child’s care and the broader familial context—both before the test is performed and, ideally, to be reviewed again before result disclosure.
GCs may often be involved in pretest counseling regarding germline testing—at least at well resourced hospitals. However, because somatic testing can unintendedly identify possible germline variants, one might argue that GCs would have a valued role in pretest counseling in that setting as well. Unfortunately, there is a relative paucity of genetics professionals.
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This, as well as challenges with time limitations in the setting of sending tumor testing, may make this logistically challenging. This resource gap is further magnified in the research setting, in which informed consent is frequently obtained by clinical research associates or study coordinators who may lack specialized training in genomic medicine or counseling techniques. For instance, the MCI protocol allows for consent to be performed by research staff despite the inclusion of comprehensive germline analysis for both pediatric and adult‐onset cancer‐predisposition genes.
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This reliance on nonclinical research staff, although necessary for the logistics of trial enrollment, can result in suboptimal pretest communication and may leave families underprepared for the profound hereditary implications of the findings.

Return of results
Several challenges commonly also arise around the return of genomic results. Specifically, uncertain or unexpected results can complicate communication with patients and their families. Especially when large cancer gene panels are used, there may be secondary findings—results that were queried but are presumably unrelated to the cancer diagnosis.
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For instance, the unexpected identification of a BRCA1 variant may result from tumor genomic sequencing. In more extensive sequencing, there also may be incidental findings—results that were not specifically queried and are presumably unrelated to the cancer diagnosis.
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For example, whole‐exome sequencing performed in the context of a new cancer diagnosis in a child may uncover a gene that identifies an increased risk of early onset Alzheimer disease. The presence of a VUS further complicates the communication of results. Some posit that this spectrum of uncertain or unexpected findings is best managed when the patient and family know that these results may be possible before receiving such results.
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Even when discussed as possibilities with a patient or family at the time that testing is sent, these results can spur a range of emotions, including confusion or distress.
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Beyond the complexity of the results themselves, emerging data indicate that many parents lack clear understanding of the genomic information returned to them. In pediatric oncology, whereas most parents recall the result, many remain confused about the distinction between somatic and germline testing and the nuances of a VUS.
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This lack of clarity may be rooted in part in the informational and emotional overload of a new cancer diagnosis, which can hinder the processing of complex data.
Although we describe the identification of secondary or incidental findings or a VUS as challenges, for some patients and their families, these findings may be perceived as positive—an example of the psychosocial utility of genomic testing.
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For instance, the family of a teenager with acute myeloid leukemia who also has a BRCA1 variant identified on her diagnostic bone marrow specimen (somatic), which is then confirmed on skin fibroblast testing (germline), may describe relief to have identified this secondary finding before she enters adulthood and to have the opportunity for family members to also undergo testing. This psychosocial utility may also be seen even when only a VUS is identified. A family may describe the genomic testing as having provided reassurance that they have done everything to understand their child’s cancer.
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There are growing data indicating that patients and parents lack clarity about the results returned to them through testing—both germline and somatic.
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Families, of course, may differ in their views on receiving genetic testing information. Although most people would like to receive all genomic data—both related and unrelated to the cancer diagnosis—there are some individual families who would prefer not to receive particular types of information, such as that unrelated to the cancer or uncertain or unactionable data.
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This highlights the importance of thoughtful pretest counseling and personalization of care, particularly when the tests are not integral to upfront management of the cancer.
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When thorough pretest counseling occurs, patients and families may agree to proceed with testing but may choose not to receive certain categories of results (e.g., secondary findings). Although this respects their autonomy, it creates practical challenges. Increasing transparency of electronic health records through patient portals requires careful consideration of how and where declined results are documented to prevent inadvertent disclosure. In addition, when families opt out of receiving some or all available results, it can place an emotional, ethical, and cognitive burden on those who still hold that information—whether laboratory staff, GCs, molecular geneticists, or pediatric oncologists—who must balance obligations of confidentiality and veracity while remembering not to disclose potentially clinically relevant findings that the family has opted not to receive.
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These challenges underscore the need for clear institutional policies and safeguards, such as protocols for flagging declined results and preventing automatic release in electronic records.
For both the delivery of genomic testing results and their management, GCs are integral parts of the modern pediatric oncology care team. Integrating a GC into a clinical team, such as into a multidisciplinary brain tumor clinic that also includes neurosurgery, oncology, and endocrinology, may allow for more cross‐discipline communication and may facilitate follow‐up genetic counseling when needed.
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Effective multidisciplinary models require trust between professional groups and clear role delineation. Across institutions, the model of care may differ based on clinical program structures and resources available to support different models. Along with this variation in models, the timing of integrating a GC into the care of a child with cancer is not standardized across centers or even within some institutions. Notably, differential access to GCs and genetic counseling services is another locus of potential disparities, as described more fully above.
As the rapidly changing landscape of genomics continues to evolve, variants identified on testing today may carry different relevance in years to come. Furthermore, the mechanisms of testing continue to become more advanced and sensitive, allowing the same biospecimen to potentially reveal new findings years later. Questions remain of how often genomic testing results should be re‐analyzed or when a tumor or germline specimen should be re‐tested. These are especially relevant questions in the pediatric population—a group with higher survival rates than adult patients with cancer. A VUS identified today may later be reclassified as pathogenic—often years after diagnosis, when most children with cancer will still be alive—heightening the importance of ongoing genomic data re‐analysis.
This presents the added challenge of who is responsible for following up (i.e., who should re‐analyze genomic data in light of new developments and how frequently this should be done), for how long (e.g., in perpetuity, until the child reaches adulthood, until the child dies, etc.), and how to design a return‐of‐results process that prioritizes the psychosocial and psychological safety of the patient and family.
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Central to these considerations is the logistical hurdle of resourcing the re‐contacting of patients, some of whom may have physically moved to a new state or country.
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This issue is particularly acute when genomic data are generated within research frameworks, because these initiatives are typically supported by time‐limited grants that may not provide the long‐term funding or infrastructure necessary to re‐engage families years or even decades after the initial testing was performed.
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As a child ages and transitions to the adult medical care system—and may have a range of understanding of the details of their medical care during childhood—this may be even more ethically and logistically complex.
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Another important practical and ethical challenge arises when genomic sequencing results become available after a patient’s death. Clinicians should approach communication of these results thoughtfully, recognizing that disclosure may influence a family’s grieving process—potentially providing closure or, conversely, causing additional distress. Although institutional policies vary, professional guidelines generally suggest that the decision to disclose posthumous results should be guided by the clinical actionability of the findings for surviving relatives. Ethical frameworks often prioritize the disclosure of germline variants that carry significant health implications for family members—such as those on the American College of Medical Genetics and Genomics highly actionable list—because of a perceived duty to warn relatives of preventable risks.
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Conversely, there is less consensus regarding the disclosure of purely somatic findings or a VUS, in which the potential for psychological distress may outweigh the clinical utility of disclosure of such findings after the patient’s death. Ideally, preferences for posthumous disclosure should be established during the initial pretest informed‐consent process; however, in the absence of such documentation, clinicians must balance the relatives' right to know potentially relevant and/or actionable information against the deceased patient's privacy and the family's right not to know. Clear institutional guidance is essential to help clinicians navigate these competing interests, ensuring that, when disclosure occurs, it is accompanied by access to genetic counseling and psychosocial resources to support the family through the medical and emotional implications of the data.
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Another key ethical challenge emerges when pediatric patients who previously contributed genomic data reach the age of majority and gain legal authority regarding their own health care information. This transition complicates the balance between the benefits of data sharing and the need to safeguard privacy and support autonomous decision‐making. Although relevant for patients of all ages, it is specifically important to consider when children reach the age of majority—18 years for most areas of the United States. Many adolescent and young adult patients with cancer endorse desiring a re‐consent process for studies on which they enrolled before the age of majority, particularly those related to genomic testing.
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This may be logistically difficult if research participants are unable to be reached.
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If an adult participant does not consent, their genomic data obtained while they were a minor may have already been submitted to a central repository or bank, and/or it may have already been integrated into other data sets. Genomic data can be unlinked from other personal health information, like clinical information or age; however, given the nature of the data, they can never truly be de‐identified. Furthermore, it can be challenging to fully remove genomic data from repositories or data sets once that data have been included. In pediatric oncology, these challenges highlight the need for policies and practices that—as best as is feasible—safeguard patient privacy, respect the autonomy of adolescents transitioning to adulthood, and ensure that genomic data collected during childhood are used ethically and responsibly. And, when it is not feasible to completely remove genomic data from a database or other repository at a young adult patient’s request (and/or if those data have already been used and thus involvement in the study cannot fully cease even at the young adult’s request), that should be communicated clearly, transparently, and compassionately.

GENOMIC ADVANCES AND OTHER EMERGING TECHNOLOGIES
It is important to recognize that emerging genomic technologies are a complement to, rather than a replacement for, established treatment modalities. In pediatric oncology, many standard regimens already achieve excellent outcomes. In the absence of compelling evidence, genomic findings alone should not drive an immediate departure from proven, efficacious approaches. For instance, even when a targetable alteration is identified in a highly curable cancer, such as localized, favorable histology Wilms tumor, caution is warranted before substituting a well validated regimen for a novel therapy supported by limited data.
This balance—between rapid integration of promising advances and appropriate restraint to avoid premature changes to standard care—remains a central challenge, particularly for settings in which pediatric oncology clinicians may be less familiar and/or comfortable with cancer genomics. The history of bone marrow transplantation for metastatic breast cancer underscores the risks of acting on immature data; early uncontrolled studies and strong biologic rationale led to widespread adoption and insurance mandates before randomized trials ultimately demonstrated no survival benefit and significant toxicity.
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Even well intentioned changes in practice ultimately may cause harm at the individual and societal level if those changes are not instituted in a cautious, data‐driven fashion. Conversely, the decisional calculus likely differs for diseases with very poor prognoses and limited treatment options, such as diffuse intrinsic pontine glioma or relapsed rhabdomyosarcoma. In such settings, given a lack of evidence‐based options, it may be reasonable to integrate genomically informed findings into clinical care even without robust, long‐term data, if desired by the patient/family. In these scenarios, data on patient quality of life are invaluable to inform these complex decisions, as is a robust process of shared decision‐making.
Circulating tumor DNA (ctDNA) is an emerging tool that presents both opportunities and ethical considerations. ctDNA may facilitate diagnosis when biopsy is challenging, enable longitudinal monitoring for tumor response during therapy, and aid in detection of recurrence after treatment completion.
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However, pediatric data remain limited, and further study is needed before routine clinical implementation.
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Notably, the utility of ctDNA is an area of active study across multiple pediatric cancers through the COG and other research consortia.
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The psychological and ethical implications of incorporating ctDNA into clinical monitoring warrant careful consideration. Although it may provide additional information, the lack of standardized interpretation—particularly for low‐level findings—may exacerbate parental distress and uncertainty regarding tumor response or recurrence. Like other genomically informed technologies, determining the threshold of evidence for integration into routine practice remains challenging.
Another novel advance, direct‐to‐consumer (DTC) genetic testing, has become widely available over the past 2 decades. Whereas most DTC tests, such as that provided by 23andMe, are not designed for children, samples from minors may be submitted with parental consent/permission. Notably, DTC platforms typically bypass the traditional pretest counseling process common in clinical genetics, relying instead on digitized educational materials and automated consent interfaces that may not adequately prepare families for the emotional weight or scientific complexity of the findings.
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Such results may reveal personal or familial cancer predisposition (e.g., BRCA1 and BRCA2) or other unanticipated findings, such as misattributed paternity.
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Pediatric oncologists may increasingly encounter patients or families who have obtained such information outside the clinical setting, raising questions about interpretation, counseling, and follow‐up.
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Regarding interpretation, DTC reports have been shown to have high rates of false positives and inaccurate variant classification. There are documented instances of patients pursuing irreversible clinical actions, such as prophylactic surgeries, based on unverified DTC findings that were later identified as benign or common variants.
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Furthermore, because families must rely solely on automated reports without professional guidance, they lack the counseling necessary to contextualize the findings that is part of the standard of care in clinical testing.
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Finally, the absence of a formal provider relationship means that families do not benefit from the longitudinal obligations inherent in clinical care, such as the systematic reinterpretation of variants as new data emerge or the coordinated management of cascade testing for at‐risk relatives.
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Similarly, multicancer detection (MCD) tests are receiving significant attention. These blood‐based assays—often referred to as liquid biopsies—aim to detect molecular signals (such as DNA methylation patterns) from multiple cancer types simultaneously, ideally before clinical symptoms appear, sometimes using artificial intelligence in their predictive algorithms.
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Currently, MCD tests are primarily marketed to healthy adults and are typically accessed as clinician‐ordered, laboratory‐developed tests that are paid for out‐of‐pocket. Despite this adult focus, pediatric oncologists likely will increasingly encounter results in younger populations that require evaluation. The challenge is that these tests have primarily been studied in adults, with uncertain performance in children and a high potential for false positives that could lead to unnecessary investigations or anxiety.
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Multiple studies are ongoing to assess the overall utility of MCD tests, but mature data in this area likely will not be available for some time.
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In addition to clinical challenges, DTC and MCD tests also raise concerns about privacy and data ownership. Recent debates—for example, around 23andMe’s bankruptcy and the possibility of consumer data being sold to third parties—highlight the uncertainty around how genomic information is stored, used, and shared.
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These issues are particularly complex for pediatrics, in which parental permission governs data submission but the child’s own consent or assent regarding the long‐term use of their genetic data is initially absent. This creates a unique ethical vulnerability because the child’s right to self‐determination remains in flux until they reach the age of majority, at which point they may choose to withdraw consent for the continued storage or use of their data.
Finally, advances in genetic modification technologies, including gene editing, have transformative potential for pediatric hematology and oncology, particularly for conditions such as sickle cell disease and other hemoglobinopathies.
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However, these approaches bring unique ethical concerns about long‐term safety, costs, and equitable access.
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Together, these technologies underscore the need for ongoing ethical, clinical, and policy evaluation before widespread integration into pediatric care.

IMPLICATIONS FOR CLINICAL PRACTICE AND NEXT STEPS OF STUDY

Guidance
The expanding role of genomic testing in pediatric oncology requires clear guidance to support both clinicians and families. Pediatric oncology clinicians face not only technical and logistical challenges associated with genomic testing but also ethical and psychosocial complexities unique to caring for children with cancer and their families. Therefore, effective guidance must address communication and counseling, data handling and documentation, equitable access to testing, and longitudinal follow‐up throughout the cancer trajectory (Table 3).
Pediatric oncology clinicians have a professional duty to maintain competency in the tools and practices that shape day‐to‐day patient care. As genomic sequencing becomes increasingly embedded in diagnostic and therapeutic decision‐making, clinicians must develop and sustain a working proficiency in genomics, including an understanding of when testing is indicated, how results should be interpreted, and what institutional and national resources are available to support these processes. Programs should ensure this competency through formal fellow education and ongoing maintenance of certification. Because no single oncology clinician can be expert in all facets of genomic medicine, interdisciplinary models are essential. Whenever feasible, GCs should be embedded within pediatric oncology practices, and/or strong partnerships with genetics services should be established to ensure consistent, accurate counseling for patients and families.
At the systems level, standardized clinical pathways are needed to reduce variability across institutions and achieve consistency in patient care. These pathways should clarify when tumor‐only versus paired tumor–germline testing is appropriate, what types of panels should be prioritized for pediatric rather than adult populations, and how results—including VUS and incidental findings—should be documented and disclosed. Such standardization not only will support clinician decision‐making but also will help build evidence.
Finally, equity must be a guiding principle in the development and implementation of genomic testing guidelines. Access to genomic testing should not be contingent on receiving treatment at highly resourced centers. Ensuring equitable availability—through funding mechanisms, integration into cooperative research protocols, and genetic counseling through telehealth—will be critical to realizing the full potential of genomics in pediatric oncology without exacerbating existing disparities.
Across all these efforts, a patient‐centered and family‐centered approach remains essential. Just as genomic testing allows for more individualized treatment, communication and decision‐making should be tailored to each child and their family’s needs, preferences, and goals. Thoughtful, personalized interactions—ranging from the pace and timing of discussions to the selection of which results are emphasized—help ensure that testing is goal‐concordant, interpretable, and supportive, complementing the technical advances of genomic medicine with a parallel commitment to ethical, effective, and compassionate care.

Future areas of study
Looking forward, several key areas warrant attention in future research on pediatric genomic testing, spanning ethical considerations, communication practices, and the inclusion of diverse pediatric perspectives (Table 4). Research in this area should broaden the focus beyond young adults and parental perspectives to intentionally include the experiences and voices of adolescents and, when feasible, younger children.
Efforts to standardize communication approaches—including shared language, timing, content of counseling, and role responsibilities on multidisciplinary teams—will be critical to reduce variability across institutions and promote consistent, family‐centered practice. Advancing equity in genomic research participation remains a priority. This must include strategies to ensure linguistic accessibility, such as the consistent use of professional medical interpreters and the availability of high‐quality, translated educational and consent materials. Beyond these immediate tools, broader community engagement and culturally tailored communication may help address disparities and ensure that underrepresented populations benefit from genomic advances.
Longitudinal responsibilities also require systematic study, including how best to recontact patients as variants are reclassified, how reconsent should be managed as minors transition into adulthood, and what mechanisms may be feasible for reanalysis or retesting over time. Finally, studies should examine how genomic data inform care, moving beyond broad notions of utility to understand the specific ways results shape treatment trajectories, clinical decision‐making, and long‐term outcomes for children and their families. Together, these priorities underscore the need for research that not only advances genomic science but also strengthens its ethical and patient‐centered integration into pediatric oncology.

CONCLUSION
Pediatric genomic testing holds significant potential to improve outcomes, but its promise can only be realized through careful attention to ethical, psychosocial, and equity considerations. Pediatric oncology clinicians must remain competent in genomic medicine, integrate interdisciplinary support, and make progress in standardizing communication practices and clinical pathways to ensure accurate interpretation and consistent discussions with patients and families. Research must broaden to include additional perspectives, address longitudinal challenges, and clarify the real‐world impact of genomic data on treatment decisions. By proactively addressing these issues, the pediatric oncology community can make use of genomic advances thoughtfully, responsibly, equitably, and in a manner that truly benefits children and their families.

CONFLICT OF INTEREST STATEMENT
Jonathan M. Marron reports grants/contracts from the Conquer Cancer Foundation, the National Institutes of Health, and the Palliative Care Research Cooperative Group; honoraria from Partner Therapeutics for serving on their Ethics Advisory Board; personal/consulting fees from Sanofi and Genzyme US Companies; lecture fees from Sanofi‐Genzyme Global Oncology; fees as an expert witness from Trentalange & Kelley, PA, and Arnett, Draper, & Hagood, LLP; and holds stock in ROMTech outside the submitted work. Brittany L. Greene disclosed no conflicts of interest.