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BRCA2 c.156_157insAlu Founder Variant in Northern Portugal: An Insight Into Hereditary Breast and Ovarian Cancer Genetic Risk and Management.

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Clinical genetics 2026 Vol.109(2) p. 327-334
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Duarte SAC, Arantes R, Martins M, Moutinho O, Queiroga FL, Pinto-Leite R

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The BRCA2 c.156_157insAlu variant is a Portuguese founder mutation implicated in hereditary breast and ovarian cancer (HBOC).

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APA Duarte SAC, Arantes R, et al. (2026). BRCA2 c.156_157insAlu Founder Variant in Northern Portugal: An Insight Into Hereditary Breast and Ovarian Cancer Genetic Risk and Management.. Clinical genetics, 109(2), 327-334. https://doi.org/10.1111/cge.70046
MLA Duarte SAC, et al.. "BRCA2 c.156_157insAlu Founder Variant in Northern Portugal: An Insight Into Hereditary Breast and Ovarian Cancer Genetic Risk and Management.." Clinical genetics, vol. 109, no. 2, 2026, pp. 327-334.
PMID 40815108 ↗
DOI 10.1111/cge.70046

Abstract

The BRCA2 c.156_157insAlu variant is a Portuguese founder mutation implicated in hereditary breast and ovarian cancer (HBOC). This study aims to determine its occurrence and clinical implications in the northern interior region of Portugal. A retrospective study of 571 individuals referred for HBOC genetic counseling and testing between 2021 and 2024 was conducted. Genetic screening was performed using next-generation sequencing of 27 hereditary cancer genes, with confirmatory PCR for BRCA2 c.156_157insAlu. Pathogenic or likely pathogenic variants were detected in 19.8% of participants, with BRCA1/2 variants accounting for 5.4%. The BRCA2 c.156_157insAlu variant was identified in 6 individuals (25% of all BRCA2 pathogenic variants identified), including breast cancer patients and asymptomatic carriers. Clinically, it was associated with early onset and contralateral breast cancer. Cascade testing and genetic counseling were offered to at-risk relatives. The BRCA2 c.156_157insAlu variant remains a significant contributor to HBOC in northern Portugal. Its high local proportion among BRCA2 variants supports the implementation of targeted genetic testing strategies, enhancing early detection and personalized cancer risk management.

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