BRCA1 and BRCA2 Mutations in an Asian Clinic-based Population Detected Using a Comprehensive Strategy

Abstract

Background and objective: Genetic testing for germ line mutations in the BRCA1 and BRCA2 genes for some families at high risk for breast and/or ovarian cancer may yield negative results due to unidentified mutations or mutations with unknown clinical significance. We aimed to accurately determine the prevalence of mutations in these genes in an Asian clinicbased population by using a comprehensive testing strategy. Materials and Methods: Ninety-four subjects from 90 families were accrued from risk assessment clinics. In addition to conventional mutational screening of BRCA1 and BRCA2, multiplex ligation-dependent probe amplification for the detection of large genomic rearrangements, evaluation of splice site alterations using transcript analysis and SpliceSiteFinder prediction, and analysis of missense mutations of unknown significance by multiple sequence alignment, PolyPhen analysis, and comparison of Protein Data Bank structures were incorporated into our testing strategy.

Prevalence ofBRCA1andBRCA2Germline Mutations in Breast Cancer Women of Multiple Ethnic Region in Northwest China

“…The results are consistent with the previous reports [3,15-17], showing BRCA2 mutation may not be less prevalent at least in some Asian populations. In contrast, in most published data from the Caucasian population, BRCA1 germline mutation is more prevalent than BRCA2 [18]. One pathogenic BRCA mutation (1/16, 6.25%) was detected among 16 bilateral cancer cases.…”

Increased ID4 expression, accompanied by mutant p53 accumulation and loss of BRCA1/2 proteins in triple‐negative breast cancer, adversely affects survival

“…Loss of both BRCA1 and BRCA2 protein expression was observed to be significantly high in our TNBC patient population, with loss of BRCA2 being higher (90%) (Table ). In a cohort of Singaporean women assessed at a risk assessment clinic, BRCA1 and BRCA2 mutations were found in 6.7 and 8.9% of cases, respectively . However, reports indicate that up to 48% of BRCA1 mutation carriers are TNBC patients .…”

“…In a cohort of Singaporean women assessed at a risk assessment clinic, BRCA1 and BRCA2 mutations were found in 6.7 and 8.9% of cases, respectively. 47 However, reports indicate that up to 48% of BRCA1 mutation carriers are TNBC patients. 48 Taken together, it can be inferred that BRCA1 and BRCA2 mutations are more common in TNBC.…”

Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation

“…Dutch [18] Italian [23,31,32] Aus/NZ [15] Asian [77,87] Hispanic [41] Czech [47] Greek [29] German [30] French [58] Spanish [28] Portuguese [88] Danish [68] N. Poland [89] Finnish [35][36][37] Fr/Can [19] Iranian [20] Table 2 of the paper they state it will result in a stop In the following section, we attempt to explain in more depth and clarify any misunderstandings regarding the HGVS nomenclature as described by den Dunnen and Antonarakis [27]. First, when describing a deletion, the incorrect bases are often used as the breakpoints.…”