Genetic testing strategies for diagnosing hereditary cancer syndromes: From somatic testing to germline testing with illustrative BRCA cases
Year: 2025
Type: article
Study design: Case Report
Abstract: Purpose: Conventional indication-based germline BRCA1/2 testing (e.g., early-onset, triple-negative breast, or ovarian cancer) may miss some carriers.As tumor next-generation sequencing (NGS) becomes widely used for therapeutic guidance, it can identify variants suggestive of germline origin.This study describes our single-center experience with reflex germline testing triggered by tumor BRCA1/2 results to inform diagnostic approaches to hereditary cancer syndromes. Materials and Methods:We retrospectively reviewed eight consecutive patients with tumor NGS-detected BRCA1/2 variants who were referred for post-result counseling and confirmatory germline testing, identified from among 1,076 individuals counseled at Ewha Womans University Mokdong Hospital, Seoul, Korea, between 2018 and 2025.Results: Of eight patients with tumor BRCA1/2 variants, germline testing confirmed germline status in seven, while one was tumor-only.Two had high-grade serous ovarian carcinoma, where a germline origin was expected and confirmed.Two with bladder cancer-less typically BRCA-associated-had tumor variant allele frequencies of 46-50% and matched germline variants.One patient with endometrial and synchronous high-grade serous ovarian carcinoma had a BRCA1 variant on endometrial NGS, confirmed as germline.Another patient with liver metastasis from breast cancer harbored two BRCA2 variants (variant allele frequencies 49.1% and 10.5%); germline testing classified the 49.1% variant as germline and the 10.5% as somatic.Conclusion: Tumor-based NGS can reveal clinically actionable germline BRCA1/2 variants, especially in those who would otherwise fall outside current testing criteria Reflex germline testing following tumor sequencing may expand opportunities for early diagnosis of hereditary cancers.Standardized algorithms are needed to integrate tumor-based reflex testing into routine clinical practice.
Source: Journal of genetic medicine
Authors: Min-Kyung So, Boeun Yoo, Jungwon Huh
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7117558110