BRCA1

A new alternative splice variant of BRCA1 containing an additional in-frame exon

A new alternative splice variant of BRCA1 containing an additional in-frame exon

Introduction

Breast cancer is the most common cancer affecting women in the Western world. During the past decade, a number of genes have been associated to an increased risk of breast cancer. Among these, BReast CAncer susceptibility gene 1 ( BRCA1 ) (MIM 113705) and BReast CAncer susceptibility gene 2 (BRCA2) (MIM 600185) are the two major genes causing a genetic susceptibility to breast and ovarian cancer BRCA1 protein product is involved in various fundamental cellular processes, including checkpoint control of cell cycle, DNA repair and recombination, transcriptional regulation, apoptosis and centrosome duplication. Direct sequencing of the BRCA1 gene for over 50,000 patients in North America has revealed more than 1500 genetic sequence variants to date(Fortin, et al., 2005).

They are listed in the Breast Information Core (BIC : http://www.research.nhgri.nih.gov.simsrad.net.ocs.mq.edu.au/bic/) database.

In addition, to a large amount of deleterious germline mutations occurring at splicing sites, several alternative splicing variants of the wild-type BRCA1 transcript have been detected during the cloning of the gene or the following extensive analyses using cDNA samples over the past decade. Twenty-one of the BRCA1 mRNA variants keep the original reading frame.

As for the present study, we describe here a new BRCA1 transcript generated by an in-frame insertion between exons 13 and 14, designated exon 13A, as well as its relative abundance in various normal human tissues and cancer cell lines.

Ascertainment of families and DNA samples

This study is part of a larger ongoing research program, the objective of which is to estimate the frequency and penetrance of deleterious BRCA1/ 2 alleles in high-risk French-Canadian breast/ovarian cancer families. These families were recruited according to strict criteria:

(1) families with at least four individuals with breast ...