Next-generation sequencing of BRCA1 and BRCA2 genes in Moroccan prostate cancer patients with positive family history

Abstract

Prostate cancer is the most common male cancer in Morocco. Although sporadic forms account for a large proportion of patients, familial forms of prostate cancer are observed in 20% of cases and about 5% are due to hereditary transmission. Indeed, germline mutations in BRCA1/2 genes have been associated with prostate cancer risk. However, the spectrum of these mutations was not investigated in Moroccan Prostate cancer patients. Thereby, the aim of this study was to characterize and to estimate the prevalence of germline BRCA1/2 mutations and large rearrangements in Moroccan patients with familial prostate cancer. The entire coding regions and intron/exon boundaries of BRCA1 and BRCA2 genes have been analyzed by next generation sequencing (NGS) in a total of 30 familial prostate cancer patients. Three pathogenic mutations were detected in four unrelated patients (13.3%). One BRCA1 mutation (c.1953_1956delGAAA) and two BRCA2 mutations (c.7234_7235insG and BRCA2ΔE12). In addition, sixty-three distinct polymorphisms and unclassified variants have been found. Early identification of germline BRCA1/2 mutations may be relevant for the management of Moroccan prostate cancer patients.

Deleterious and ethnic-related BRCA1/2 mutations in tissue and blood of Egyptian colorectal cancer patients and its correlation with human papillomavirus

“…This intriguing ethnic diversity indicates Egypt's unique genetic composition, situated as a transcontinental nation between the northeastern corner of Africa and the southwestern corner of Asia. Notably, previous research corroborates these findings, as the identified BRCA1 (c.4900A > G, c.2612C > T, c.3548A > G, 0.3113A > G) and BRCA2 (c.7397 T > C, c.1114A > C) clusters were observed in an earlier Egyptian study [ 67 ] as well as within Arab African populations like Algerian [ 68 ], Bahrainian [ 69 ], Moroccan [ 70 ] and Tunisian [ 71 ] groups, alongside Asian populations encompassing Chinese [ 72 ], Korean [ 73 ], Iranian [ 74 ] and Indian [ 75 ] cohorts, and even in American and European populations such as Brazilian [ 76 ], and Italian [ 77 ] ones, respectively. This reinforces the intricate interplay of various ethnic backgrounds shaping the genetic landscape of Egypt.…”

Screening of BRCA1/2 variants in Mauritanian breast cancer patients

“…The second pathogenic variant (c.4986 + 6 T > C) in BRCA1 carried by seven of our BC patients has also been detected in multiple African patients with an early-onset of BC [ 34 , 35 ]. This splicing site variant is located in highly conserved human genome region and seems to activate a cryptic splice donor site which alters the reading frame resulting in absent or truncated protein [ 36 , 37 ]. It was proposed by ClinVar as pathogenic germline allele by numerous submitters [ 35 , 38 ].…”

Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer

“…The DNA damage repair (DDR) process uses non-conservative and potentially mutagenic methods when these BRCA1 and/or BRCA2 genes are absent. There is evidence that this genomic instability contributes to the cancer risk associated with harmful BRCA gene mutations ( Salmi et al, 2021 ). BRCA1 and BRCA2 pathogenic mutation carriers have a relative risk of PCa that is enhanced by 1.8–3.8 and 2.5 to 8.6 times, respectively, by the time they are 65 years old ( Thompson et al, 2003 ; Agalliu et al, 2007 ; Leongamornlert et al, 2012 ).…”