Highlights
- •BCCIP is a critical component of the DNA damage response network and HRR pathway due to its interaction with BRCA2 and RAD51.
- •To our knowledge, we have performed the first mutational study of BCCIP in breast/ovarian cancer families.
- •BCCIP germ line mutations are very likely not relevant in genetic susceptibility to breast cancer in our Spanish population.
Abstract
Objective
About 5%–10% of breast cancer is due to inherited disease predisposition. Currently,
mutations in the BRCA1 and BRCA2 genes explain less than 25% of the familial clustering of breast cancer, and additional
susceptibility genes are suspected. The BCCIP gene plays an important role in the regulation of gene transcription and cell proliferation
and could be involved in the maintenance of genomic integrity. The BCCIP protein binds
in mammalian cells to the longest conserved region of the BRCA2 protein and is required
for BRCA2 stability and function, making a critical contribution to the function of
BRCA2 in mediating homologous recombination. Variants in the BCCIP gene could affect the BRCA2 functionality and be associated to the familial breast/ovarian
carcinogenesis. Therefore, BCCIP gene is a potential candidate for being involved in heritable cancer susceptibility.
Methods
We have screened the entire coding region and splice junctions of BCCIP in affected index cases from 215 Spanish breast/ovarian cancer families for germ
line defects, using direct sequencing.
Results
Mutation analysis revealed 3 different intronic sequence changes.
Conclusions
Based on the in silico and in vitro RNA analyses of these sequence alterations, none of them were predicted to be pathogenic
or associated with cancer susceptibility.
Our results indicate that BCCIP germ line mutations are unlikely to be a major contributor to familial breast/ovarian
cancer risk in our population.
Keywords
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Article info
Publication history
Accepted:
July 25,
2013
Received:
June 3,
2013
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
