Novel de novo BRCA1 mutation in a woman with early onset breast cancer

Abstract

e22143 Background: Germline mutations in BRCA1/2 account for a significant portion of hereditary breast/ovarian cancer. Mutation carriers usually have a family history of breast/ovarian cancer or early onset disease. Rarely, germline mutations are found only in the probands but not in any family members. Such de novo mutations have been reported in diseases such as hemophilia A, thalassaemia and familial adenomatous polyposis. De novo mutations in the BRCA1 or BRCA2 genes are rare and the few reported have been in BRCA2. Here, we describe de novo as well as novel mutation of the BRCA1 gene in a breast cancer patient. Methods: Blood DNA samples from a 30 year old Chinese woman with breast cancer and no family history of cancer was tested for a BRCA1/2 mutation by full gene sequencing and Multiple Ligation-dependent Probe Amplification (MLPA). Family members were analyzed for the same mutation. Paternity was determined by a set of highly polymorphic short tandem repeat (STR) markers. Results: Full gene sequencing found no deleterious mutation. MLPA revealed a large deletion of exons 1 to 12 of BRCA1 in the proband. MLPA performed on 5 family members: proband's mother and father (who were 1st degree relative- cousins), stepmother (mother's biological sister), 2 sisters (1, same parents; 1, same father and stepmother) found no similar deletion. By using a set of highly polymorphic STR markers, the proband's father and mother were confirmed to be her biological parents. Conclusions: We report a novel de novo BRCA1 deletion mutation encompassing exons 1 - 12 in a Chinese breast cancer patient of early onset with no family history. Identification of this large deletion confirms the importance of pursuing rearrangement testing if full gene sequencing fails to detect a point mutation or short insertion deletion. The mutation found in this study is de novo. This may simply be a random mutation event which occurred in the parents' germ cells during their lifetime which passed onto one of their offspring or maybe a result of gene inversion or splicing deficiency. The relations of such mutations with consanguineous marriage cannot be ruled out. Mutation screening is important in early onset breast cancer patients even if there is no family history. No significant financial relationships to disclose.