Germline BRCA2 variant with low variant allele frequency detected in tumor‐only comprehensive genomic profiling

• Published in: Cancer science 2024-02, Vol.115 (2), p.682-686
• Main Authors: Hayashi, Hideyuki, Kunimasa, Kei, Tanishima, Shigeki, Nakamura, Kohei, Ishikawa, Marin, Kato, Yasutaka, Aimono, Eriko, Kawano, Ryutaro, Nishihara, Hiroshi
• Format: Article
• Language: English
• Subjects: Alleles; BRCA; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Case Report; Gene Frequency; Genes; Genetic counseling; Genetic Predisposition to Disease; genomic loss; Genomics; Germ Cells; Germ-Line Mutation; Humans; low VAF; Mutation; Ovaries; PARP inhibitor; Patients; Prostate cancer; Sarcoma; Tumor cells; Tumors; tumor‐only CGP; Uterine cancer; Uterus
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.16043

Germline BRCA1/2 variants in comprehensive genomic profiling (CGP) often exhibit variant allele frequency (VAF) exceeding 50%. However, when genomic loss occurs at the ipsilateral allele, including the germline variant in tumor cells, the VAF is low. This case report presents a patient with uterine sarcoma with a pathogenic BRCA2 mutation and low VAF in tumor‐only CGP, which was later identified as a germline variant. When genomic alterations in BRCA1/2 are identified in tumor‐only CGP, the possible germline origin of the variants should be considered, even if their VAF is very low. This is a case of a tumor with a germline BRCA2 variant with BRCA2 loss at the ipsilateral allele, and the tumor cellularity determined by the pathologist was 95%. The estimated variant allele frequency of BRCA2 was 4.8%, owing to BRCA2 loss occurring at the ipsilateral allele, including the germline BRCA2 variant.