High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.
1/5 보강
ℹ️ 이 논문은 무료 전문이 아직 없습니다. 코퍼스 전체의 43.9%는 무료 가능 (통계 →) · 🏥 기관 EZproxy로 시도
[INTRODUCTION] Rare, deleterious germline variants are key contributors to inherited lung cancer (LC) risk.
APA
Liu Y, Li Y, et al. (2025). High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 103534. https://doi.org/10.1016/j.jtho.2025.12.004
MLA
Liu Y, et al.. "High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2025, pp. 103534.
PMID
41390056 ↗
Abstract 한글 요약
[INTRODUCTION] Rare, deleterious germline variants are key contributors to inherited lung cancer (LC) risk. The Genetic Epidemiology of LC Consortium (GELCC) has curated valuable high-risk LC families and is uniquely positioned to uncover rare, high-penetrance variants underlying familial LC (FLC).
[METHODS] We performed whole-genome and exome sequencing on germline DNA from 120 high-risk LC families (177 FLC cases, 309 unaffected relatives). We prioritized rare (allele frequency <1% in the genome aggregation database), potentially deleterious variants present in two or more FLC cases. These variants were then validated in 10,085 sporadic LC (SLC) cases and 612,970 controls.
[RESULTS] We identified 118 candidate variants, 28 of which were validated in SLC with strong statistical support. We discovered a novel pathogenic axis of three truncating variants in GALNT6, MUC4, and ERBB3 genes, which are critical regulators of mucin-type O-glycosylation. Nine top hits were mapped to the known 6q23-25 linkage region (ROS1, LAMA2, PRKN, SYNE1). Other candidates were clustered in DNA repair (ATM, BRCA2, MLH1), oncogenic signaling (ERBB3, JAK1, PIM1), and extracellular matrix genes (COL6A3, FLG). Carriers of two or more variant alleles had a strong dose-dependent risk. Furthermore, gene-based burden tests revealed strong associations between RARB, MGMT, and EBF1 with FLC susceptibility.
[CONCLUSION] Our findings underscore the important role of rare, high-penetrance genetic variants in FLC susceptibility, particularly in mucin glycosylation and DNA repair genes. These findings offer promising targets for early detection and personalized therapies.
[METHODS] We performed whole-genome and exome sequencing on germline DNA from 120 high-risk LC families (177 FLC cases, 309 unaffected relatives). We prioritized rare (allele frequency <1% in the genome aggregation database), potentially deleterious variants present in two or more FLC cases. These variants were then validated in 10,085 sporadic LC (SLC) cases and 612,970 controls.
[RESULTS] We identified 118 candidate variants, 28 of which were validated in SLC with strong statistical support. We discovered a novel pathogenic axis of three truncating variants in GALNT6, MUC4, and ERBB3 genes, which are critical regulators of mucin-type O-glycosylation. Nine top hits were mapped to the known 6q23-25 linkage region (ROS1, LAMA2, PRKN, SYNE1). Other candidates were clustered in DNA repair (ATM, BRCA2, MLH1), oncogenic signaling (ERBB3, JAK1, PIM1), and extracellular matrix genes (COL6A3, FLG). Carriers of two or more variant alleles had a strong dose-dependent risk. Furthermore, gene-based burden tests revealed strong associations between RARB, MGMT, and EBF1 with FLC susceptibility.
[CONCLUSION] Our findings underscore the important role of rare, high-penetrance genetic variants in FLC susceptibility, particularly in mucin glycosylation and DNA repair genes. These findings offer promising targets for early detection and personalized therapies.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
같은 제1저자의 인용 많은 논문 (5)
- Breast Morphological Comparison Between Anatomic and Round Implant Augmentation: A Prospective Study.
- Latent transforming growth factor beta binding protein 1 (LTBP1): roles as a multifunctional extracellular matrix regulator in human disease - from molecular mechanisms to clinical translation prospects.
- Association between body mass index and outcomes in lymphoma-associated haemophagocytic lymphohistiocytosis: A retrospective multicentre cohort study of Jiangsu Cooperative Lymphoma Group (JCLG).
- Single-cell and spatial transcriptome analysis of breast cancer tumor-associated fibroblast heterogeneity and its mediated remodeling of the tumor microenvironment.
- Spatial omics at the forefront: emerging technologies, analytical innovations, and clinical applications.
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
- Reforming the delivery of smoking cessation: a distributional cost-effectiveness analysis of providing smoking cessation as part of targeted lung cancer screening.
- A herbal formulation inhibits growth and survival of lung cancer cells through DNA damage and apoptosis - in vitro and in vivo studies.
- Negative trial but positive lesson: reframing immunotherapy resistance from one-size-fits-all to precision strategies.
- Lung Cancer Screening in Adults: State-of-the-Art and Policy Mapping (2025).
- Retrospective dosimetric evaluation of the collapsed cone, AAA, and Acuros XB algorithms for lung cancer Halcyon VMAT plans.
- Metastatic Pancreatic Adenocarcinoma with Germline BLM and Somatic ATM Mutations: A Case Report and Review of DNA Damage Response.