Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Hum Mutat. 2013 Jan;34(1):70-3. doi: 10.1002/humu.22206. Epub 2012 Oct 11.
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.
SLX4/FANCP 是最近发现的范可尼贫血（FA）的一种新型疾病基因，FA 是一种罕见的隐性疾病，其特征是染色体不稳定和癌症易感性增加。在杂合突变携带者中，有三个 FA 基因是乳腺癌易感基因——BRCA2、PALB2 和 BRIP1。为了研究 SLX4 的缺陷是否也易患乳腺癌，我们对 729 例 BRCA1/BRCA2 阴性家族性乳腺癌病例的该基因进行了测序。我们发现了一个单一的剪接位点突变（c.2013+2T>A），该突变通过跳过外显子 8 导致移码。我们还鉴定了 39 个错义变体，其中 4 个被选择用于丝裂霉素 C 诱导的生长抑制测定中的功能测试，结果与野生型没有区别。虽然这是第一项描述乳腺癌患者截断 SLX4 突变的研究，但我们的数据表明，SLX4 种系突变非常罕见，不太可能对家族性乳腺癌有显著贡献。
