Analysis of the Novel Fanconi Anemia Gene SLX4/FANCP in Familial Breast Cancer Cases

作者：Bakker Janine L; van Mil Saskia E; Crossan Gerry; Sabbaghian Nelly; De Leeneer Kim; Poppe Bruce; Adank Muriel; Gille Hans; Verheul Henk; Meijers Heijboer Hanne; de Winter Johan P; Claes Kathleen; Tischkowitz Marc; Waisfisz Quinten^*

来源：Human Mutation, 2013, 34(1): 70-73.

DOI：10.1002/humu.22206

• familial breast cancer
• SLX4
• Fanconi anemia
• FANCP
• predisposition

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%26gt;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. Hum Mutat 34:70-73, 2013.

• 出版日期2013-1