Characterization of a novel large deletion and single point mutations in the BRCA1gene in a Greek cohort of families with suspected hereditary breast cancer

Abstract

Background: Germline mutations in BRCA1 and BRCA2 predispose to breast and ovarian cancer. A multitude of mutations have been described and are found to be scattered throughout these two large genes. We describe analysis of BRCA1 in 25 individuals from 18 families from a Greek cohort.

Greek BRCA1 and BRCA2 mutation spectrum: two BRCA1 mutations account for half the carriers found among high-risk breast/ovarian cancer patients

“…Three novel large genomic deletions have been found in five Greek families, del4174Ex20, del4429ins5Ex24 [18] and del3.2kbEx20 [14]. Our cumulative data indicate that large genomic rearrangements constitute a significant portion of deleterious alterations of the BRCA1 gene in the Greek population (11%, 5/46).…”

“…This work concludes our effort to obtain a more complete picture of the BRCA1/BRCA2 mutation spectrum in the Greek population. Our present data were combined with previously published results involving 160 families [11][12][13][14]18], which were recruited in the same manner and selected using the same criteria as here.…”

“…On the other hand, other countries appear to exhibit a much broader BRCA1/2 mutation spectrum. This seems to be the case of Greece, where previous studies involving breast-ovarian cancer families showed that BRCA1 5382insC is in fact the most prevalent mutation, with a number of other deleterious mutations found in parallel once or at a very low frequency [11][12][13][14]. Consequently, there is a need to perform BRCA1/ 2 screening on a large number of Greek breast/ovarian cancer families to narrow down the number of mutations to those that are biologically significant for this particular ethnic group.…”

Identification of a novel BRCA1 large genomic rearrangement in a Spanish breast/ovarian cancer family

“…Thus, it has been reported in the BRCA1 gene alterations such as the ones found in the promoter and untranslated regions (UTRs and intronic sequences) but more frequent are the large genomic rearrangements (LGRs) that disrupt the gene causing the synthesis of an aberrant protein [3][4][5][6]. Indeed, the incidence of these BRCA1 LGRs in families with strong family history of breast (BC) and/or ovarian cancer (OC) ranges from 0.8 to 23%, what represents between 8 and 40% contribution to the BRCA1 mutation spectrum in the different ethnic groups [7][8][9][10][11][12][13].…”

New sequence variants in BRCA1 and BRCA2 genes detected by high-resolution melting analysis in an elderly healthy female population in Croatia

“…The conserved BRC repeats region (Figure 4) is essential for the BRCA2 protein function in DNA repair and contains the ovarian cancer cluster region (OCCR, bounded by nucleotides 3059-4075 and 6503-6629) that is associated with ovarian cancer family history (41). Mutations in the BRC repeats are common in Japanese, Indian, German, Greek and Korean breast and ovarian cancer patients (26,27,36,(42)(43)(44). However, in this region we found 15 different variants in the healthy Croatian population, although most of them with low incidence (the exceptions were two synonymous variants).…”