Novel BRCA1 and BRCA2 pathogenic mutations in Slovene hereditary breast and ovarian cancer families

Abstract

The estimated proportion of hereditary breast and ovarian cancers among all breast and ovarian cancer cases is 5–10%. According to the literature, inherited mutations in the BRCA1 and BRCA2 tumour-suppressor genes, account for the majority of hereditary breast and ovarian cancer cases. The aim of this report is to present novel mutations that have not yet been described in the literature and pathogenic BRCA1 and BRCA2 mutations which have been detected in HBOC families for the first time in the last three years. In the period between January 2009 and December 2011, 559 individuals from 379 families affected with breast and/or ovarian cancer were screened for mutations in the BRCA1 and BRCA2 genes. Three novel mutations were detected: one in BRCA1 - c.1193C>A (p.Ser398*) and two in BRCA2 - c.5101C>T (p.Gln1701*) and c.5433_5436delGGAA (p.Glu1811Aspfs*3). These novel mutations are located in the exons 11 of BRCA1 or BRCA2 and encode truncated proteins. Two of them are nonsense while one is a frameshift mutation. Also, 11 previously known pathogenic mutations were detected for the first time in the HBOC families studied here (three in BRCA1 and eight in BRCA2). All, except one cause premature formation of stop codons leading to truncation of the respective BRCA1 or BRCA2 proteins.

A Comprehensive Focus on Global Spectrum ofBRCA1andBRCA2Mutations in Breast Cancer

“…Additionally, c.7806-2A>G and c.5291C>G are only defined in Slovenian populations, and c.7806-2A>G and IVS16-2A> were considered as a founder mutation of this region [ 83 , 85 ]. In an assay on 379 HBOC Slovenian families, c.181T>G, c.1687C>T, and c.844_850dupTCATTAC were the most frequent BRCA1 mutations while c.7806-2A>G splicing alteration which was found in 13 families was the most BRCA2 one [ 86 ].…”

Characterization of medulloblastoma in Fanconi Anemia: a novel mutation in the BRCA2 gene and SHH molecular subgroup

“…Based on this evidence, we investigated BRCA2 mutational status and confirmed the presence of biallelic truncating mutations in the FA patient. The c.658_659delGT mutation occurring on BRCA2 exon 8 had been previously reported in hereditary breast/ovarian cancer cohorts (see in example [ 45 ]) and is one of the most frequently occurring in FANCD1/BRCA2 mutated FA cases [ 29 ]. The second truncating mutation, the previously undescribed c.2944_2944delA (p.Ile982Tyrfs), occurs on BRCA2 exon 11.…”

First description of a double heterozygosity for BRCA1 and BRCA2 pathogenic variants in a French metastatic breast cancer patient: A case report

“…Furthermore, the BRCA1 c.1016dupA variant is considered a Norwegian founder mutation, but has also been observed in individuals who are of French-Canadian, French, Italian or Dutch ancestry (2,(14)(15)(16). The BRCA2 c.6814delA (p.R2272Efs*8) pathogenic variant, has been identified in individuals with a personal or family history of breast and/ or ovarian cancer (17,18). The clinical presentation was advanced and unfavorable, it may raise up the possibility of a pejorative impact of either involved mutations or resulting from their association.…”