Communicated by David E. Goldgar
Analysis of the Novel Fanconi Anemia Gene SLX4/FANCP in Familial Breast Cancer Cases
Article first published online: 11 OCT 2012
© 2012 Wiley Periodicals, Inc.
Volume 34, Issue 1, pages 70–73, January 2013
How to Cite
Bakker, J. L., van Mil, S. E., Crossan, G., Sabbaghian, N., De Leeneer, K., Poppe, B., Adank, M., Gille, H., Verheul, H., Meijers-Heijboer, H., de Winter, J. P., Claes, K., Tischkowitz, M. and Waisfisz, Q. (2013), Analysis of the Novel Fanconi Anemia Gene SLX4/FANCP in Familial Breast Cancer Cases. Hum. Mutat., 34: 70–73. doi: 10.1002/humu.22206
Contract grant sponsors: The Netherlands Organisation for Scientific Research (NWO) (ZonMw/VIDI grant no. 91756341); Jewish General Hospital Weekend to End Breast Cancer; Quebec Ministry of Economic Development, Innovation and Export Trade; Jodi Taiger Lazarus Fund for Hereditary Breast Cancer Research.
- Issue published online: 20 DEC 2012
- Article first published online: 11 OCT 2012
- Accepted manuscript online: 21 AUG 2012 09:37AM EST
- Manuscript Accepted: 8 AUG 2012
- Manuscript Received: 23 APR 2012
- The Netherlands Organisation for Scientific Research. Grant Number: 91756341
- Jewish General Hospital Weekend to End Breast Cancer
- Quebec Ministry of Economic Development
- Innovation and Export Trade
- Jodi Taiger Lazarus Fund for Hereditary Breast Cancer Research
- familial breast cancer;
- Fanconi anemia;
SLX4/FANCP is a recently discovered novel disease gene for Fanconi anemia (FA), a rare recessive disorder characterized by chromosomal instability and increased cancer susceptibility. Three of the 15 FA genes are breast cancer susceptibility genes in heterozygous mutation carriers—BRCA2, PALB2, and BRIP1. To investigate if defects in SLX4 also predispose to breast cancer, the gene was sequenced in a cohort of 729 BRCA1/BRCA2-negative familial breast cancer cases. We identified a single splice site mutation (c.2013+2T>A), which causes a frameshift by skipping of exon 8. We also identified 39 missense variants, four of which were selected for functional testing in a Mitomycin C-induced growth inhibition assay, and appeared indistinguishable from wild type. Although this is the first study that describes a truncating SLX4 mutation in breast cancer patients, our data indicate that germline mutations in SLX4 are very rare and are unlikely to make a significant contribution to familial breast cancer.