Analysis of the Novel Fanconi Anemia Gene SLX4/FANCP in Familial Breast Cancer Cases |
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| Authors: | Janine L. Bakker Saskia E. van Mil Gerry Crossan Nelly Sabbaghian Kim De Leeneer Bruce Poppe Muriel Adank Hans Gille Henk Verheul Hanne Meijers‐Heijboer Johan P. de Winter Kathleen Claes Marc Tischkowitz Quinten Waisfisz |
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| Affiliation: | 1. Department of Clinical Genetics, VU University Medical Center, , Amsterdam, The Netherlands;2. Medical Research Council, Laboratory of Molecular Biology, , Cambridge, UK;3. Program in Cancer Genetics, McGill University, , Montreal, Quebec, Canada;4. Segal Cancer Centre, Jewish General Hospital, , Montreal, Quebec, Canada;5. Center for Medical Genetics, Ghent University Hospital, , Belgium;6. Department of Medical Oncology, VU University Medical Center, , Amsterdam, The Netherlands;7. Department of Medical Genetics, University of Cambridge, , Cambridge, UK |
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| Abstract: | 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. |
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| Keywords: | familial breast cancer SLX4 Fanconi anemia FANCP predisposition |
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