A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer

Abstract

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression.Electronic supplementary materialThe online version of this article (doi:10.1007/s10689-011-9429-y) contains supplementary material, which is available to authorized users.

The importance of analysis of long-range rearrangement of BRCA1 and BRCA2 in genetic diagnosis of familial breast cancer

“…One of the mutations was de novo and was only identified in a proband (TWH9701), not in any of the family members. This rare, novel de novo germline mutation was detected in an early-onset TNBC patient and resulted in downregulation of BRCA1 gene expression (20). An absence of the BRCA1 transcript was observed in case TWH61901, which was due to the deletion of exons 1-8.…”

“…All of the subjects were of Chinese origin. The selection criteria for "high-risk" included (1): had at least one first-or second-degree relative with breast and/ or ovarian cancer, regardless of age (2); were less than 45 years of age at diagnosis (3); had bilateral breast cancer (4); had triple-negative breast cancer (TNBC) or medullary type pathology (5); had at least one relative with cancers other than breast and ovarian cancer that are known to be related to BRCA mutations; or (6) they were ovarian cancer patients with a family history of breast cancer (20). All probands underwent MLPA analysis, while full gene sequencing was performed either by Sanger sequencing (until December 2012) or NGS (from January 2013 onward).…”

Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations

“…However, in this study, only one out of four cases had a negative family history (case 2). The presence of a breast cancer family history has also been described in 5 of the 11 cases of de novo BRCA1/2 mutations reported in the literature [5][6][7][8][9][10][11][12][13][14][15] (Table 1). Breast cancer family history for de novo BRCA1/2 mutation carriers can have several origins: the high frequency of breast cancer in the general population; the strong impact of family history in the inclusion criteria for BRCA1/2 genetic testing, resulting in a bias for family cancer cases; and finally, genetic heterogeneity in breast cancer.…”

“…[1][2][3] More than 3000 distinct genetic variants have been reported in these genes (BRCA1 and BRCA2 Universal Mutation Databases 4 ). Despite the large number of mutation carriers identified by means of the large number of genetic tests conducted worldwide, only six BRCA1 and five BRCA2 de novo mutations have been reported [5][6][7][8][9][10][11][12][13][14][15] (Table 1). This small number is surprising, as the de novo mutation rate can be as high as 11-25% in APC, 74% in NF1 and up to 90% in RB1.…”

Novel BRCA1 and BRCA2 genomic rearrangements in Southern Chinese breast/ovarian cancer patients

“…De novo mutations are very rare, but reported among BRCA genes [14–17]. Previously, we reported a de novo mutation in which multiple exons were deleted from BRCA1 in a Chinese breast cancer patient [18]. To date, the spectrum of LGR in Chinese population is largely unknown.…”