- •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.
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.
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.
Mutation analysis revealed 3 different intronic sequence changes.
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.
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- The complex genetic landscape of familial breast cancer.Hum Genet. 2013; 132: 845-863
- Breast cancer susceptibility: current knowledge and implications for genetic counselling.Eur J Hum Genet. 2009; 17: 722-731
- Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation.Oncogene. 2003; 22: 5784-5791
- Cancer susceptibility and the functions of BRCA1 and BRCA2.Cell. 2002; 108: 171-182
- Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2.Science. 2004; 306: 876-879
- BRCA2: breaks, mistakes and failed separations.Trends Mol Med. 2005; 11: 145-148
- Sequence fingerprints in BRCA2 and RAD51: implications for DNA repair and cancer.DNA Repair (Amst). 2003; 2: 1015-1028
- Conserved domains in the chicken homologue of BRCA2.Oncogene. 2002; 21: 1130-1134
- Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals.Mol Cell Biol. 1999; 19: 4633-4642
- Potential role of BRCA2 in a mitotic checkpoint after phosphorylation by hBUBR1.Cancer Res. 2000; 60: 1531-1535
- Interaction with BRCA2 suggests a role for filamin-1 (hsFLNa) in DNA damage response.J Biol Chem. 2001; 276: 48318-48324
- Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2.Oncogene. 2001; 20: 336-345
- TOK-1, a novel p21Cip1-binding protein that cooperatively enhances p21-dependent inhibitory activity toward CDK2 kinase.J Biol Chem. 2000; 275: 31145-31154
- BCCIP regulates homologous recombination by distinct domains and suppresses spontaneous DNA damage.Nucleic Acids Res. 2007; 35: 7160-7170
- The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair.Mol Cell Biol. 2005; 25: 1949-1957
- Abrogation of the transactivation activity of p53 by BCCIP down-regulation.J Biol Chem. 2007; 282: 1570-1576
- Roles of BCCIP in chromosome stability and cytokinesis.Oncogene. 2007; 26: 6253-6260
- BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1.Cell Cycle. 2004; 3: 1457-1462
- BCCIP is required for the nuclear localization of the p21 protein.Cell Cycle. 2009; 8: 3019-3024
- Murine Brca2: sequence, map position, and expression pattern.Genomics. 1997; 40: 234-241
- Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA.Nat Genet. 1993; 4: 239-243
- Chromosome 10 alterations in prostate adenocarcinoma (review).Oncol Rep. 1998; 5: 1329-1335
- Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas.BMC Cancer. 2009; 9: 268
- Allelic loss of sequences from the long arm of chromosome 10 and replication errors in endometrial cancers.Cancer Res. 1995; 55: 1922-1926
- Allelic loss on chromosome 10q in human lung cancer: association with tumour progression and metastatic phenotype.Br J Cancer. 1998; 77: 270-276
- Evaluation of the BRCA1 interacting genes RAP80 and CCDC98 in familial breast cancer susceptibility.Breast Cancer Res Treat. 2009; 113: 371-376
- Mutational analysis of FANCL, FANCM and the recently identified FANCI suggests that among the 13 known Fanconi Anemia genes, only FANCD1/BRCA2 plays a major role in high-risk breast cancer predisposition.Carcinogenesis. 2009; 30: 1898-1902
- Mutation screening of the MERIT40 gene encoding a novel BRCA1 and RAP80 interacting protein in breast cancer families.Breast Cancer Res Treat. 2010; 120: 165-168
- Mutation screening of the RNF8, UBC13 and MMS2 genes in Northern Finnish breast cancer families.BMC Med Genet. 2011; 12: 98
- Mutation analysis of the SHFM1 gene in breast/ovarian cancer families.J Cancer Res Clin Oncol. 2013; 139: 529-532
Accepted: July 25, 2013
Received: June 3, 2013
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.