Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer

• Published in: Cancer genetics 2022-01, Vol.260-261, p.14-17
• Main Authors: Mampel, Alejandra, Sottile, Mayra L., Denita-Juárez, Silvina P., Vargas, Ana L., Vargas-Roig, Laura M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; BRCA1; BRCA1 Protein - genetics; BRCA2; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - genetics; Carcinoma, Ductal, Breast - genetics; Double heterozygote; Female; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Heterozygote; Humans; Neoplasms, Second Primary - genetics; Pedigree; Point Mutation; Sequence Analysis, DNA; Sequence Deletion
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2021.11.003

Double heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. The proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants NM_007300.4(BRCA1):c.4201C>T (p.Gln1401Ter), and NM_000059.3(BRCA2):c.5146_5149del (p.Tyr1716fs). . The patient's son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. There are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.