Analysis of the Novel Fanconi Anemia Gene SLX4/FANCP in Familial Breast Cancer Cases. Issue 1 (11th October 2012)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Human mutation. Volume 34:Issue 1(2013:Jan.)
• Page Start: 70
• Page End: 73
• Publication Date: 2012-10-11
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22206
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p> <italic>SLX4</italic>/<italic>FANCP</italic> 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—<italic>BRCA2</italic>, <italic>PALB2</italic>, and <italic>BRIP1</italic>. To investigate if defects in <italic>SLX4</italic> also predispose to breast cancer, the gene was sequenced in a cohort of 729 <italic>BRCA1</italic>/<italic>BRCA2</italic>‐negative familial breast cancer cases. We identified a single splice site mutation (c.2013+2T&gt;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 <italic>SLX4</italic> mutation in breast cancer patients, our data indicate that germline mutations in <italic>SLX4</italic> are very rare and are unlikely to make a significant contribution to familial breast cancer.</p> </abstract>