Prevalence of FANCM germline variants in BRCA1/2 negative breast and/or ovarian cancer patients from Pakistan

AbstractThe Fanconi anemia complementation group M (FANCM) gene is a potential candidate for breast/ovarian cancer susceptibility in European populations. Here, we examined the contribution ofFANCM germline variants to hereditary breast and/or ovarian cancer in Pakistan. ComprehensiveFANCM variant screening was performed in 201BRCA1 andBRCA2 (BRCA1/2) negative Pakistani patients with and without triple-negative breast cancer (TNBC) and/or ovarian cancer, using denaturing high-performance liquid chromatography analysis (DHPLC) followed by DNA sequencing. Novel variants were tested for their potential effect on protein function using in silico tools. Reverse transcription (RT)-PCR analysis of RNA extracted from one deletion/insertion (delins) variant (p.K1780delinsNGIT) carrier and three non-carriers was performed to evaluate the impact of this variant on splicing. Furthermore, potentially functional variants were evaluated in 200 healthy female controls. A missense variant (p.V1857M) was identified in a 50-year-old TNBC patient with a family history of breast cancer. It was also identified in the index patient ´s daughter, who was diagnosed with osteosarcoma at 15 years of age. Further, one delins variant (p.K1780delinsNGIT) was identified in a 45-year-old non-TNBC patient, but not detected in her brother, who was diagnosed with Hodgkin’s lymphoma at 38 years of age. Based on in silico and RNA analys es, p.V1857M and p.K1780delinsNGIT were predicted as variants of uncerta...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research