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.

Fig. 1

Family pedigree of proband family. The proband (III-4) is indicated by an arrow

Fig. 2

MLPA probes signals and result of the analysis. Coffalyser Sample Plate Generator (S.P.G.) was used to automatically create sample plate files for MLPA analysis. Results shown that probe signals from exon 1 to 12 were significantly decreased indicating the presence of deletion across those exons

Fig. 3

BRCA1 RNA level comparison between proband and non-probands (family members and normal controls). Box plots of BRCA1 RNA expression levels a targeting the deleted region b targeting outside the deleted region of the proband and non-proband (n = 23). Expression levels (Log10 scale at Y-axis) are normalized to GAPDH. The lines inside the boxes denote the medians. The boxes mark the interval between the 25th and 75th percentiles. The whiskers denote the interval between the 10th and 90th percentiles. Statistically significant differences were determined using Mann–Whitney tests