Allele‐specific imbalance mapping identifies HDAC9 as a candidate gene for cutaneous squamous cell carcinoma. Issue 1 (16th July 2013)

• Record Type: Journal Article
• Authors: Fleming, Jessica L.; Dworkin, Amy M.; Allain, Dawn C.; Fernandez, Soledad; Wei, Lai; Peters, Sara B.; Iwenofu, O. Hans; Ridd, Katie; Bastian, Boris C.; Toland, Amanda Ewart
• Is Part Of: International journal of cancer. Volume 134:Issue 1(2014:Jan. 01)
• Page Start: 244
• Page End: 248
• Publication Date: 2013-07-16
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28339
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>More than 3.5 million nonmelanoma skin cancers were treated in 2006; of these 700, 000 were cutaneous squamous cell carcinomas (cSCCs). Despite clear environmental causes for cSCC, studies also suggest genetic risk factors. A cSCC susceptibility locus, <italic>Skts5</italic>, was identified on mouse chromosome 12 by linkage analysis. The orthologous locus to <italic>Skts5</italic> in humans maps to 7p21 and 7q31. These loci show copy number increases in ∼10% of cSCC tumors. Here, we show that an additional 15–22% of tumors exhibit copy‐neutral loss of heterozygosity. Furthermore, our previous data identified microsatellite markers on 7p21 and 7q31 that demonstrate preferential allelic imbalance (PAI) in cSCC tumors. On the basis of these results, we hypothesized that the human orthologous locus to <italic>Skts5</italic> would house a gene important in human cSCC development and that tumors would demonstrate allele‐specific somatic alterations. To test this hypothesis, we performed quantitative genotyping of 108 single nucleotide polymorphisms (SNPs) mapping to candidate genes at human <italic>SKTS5</italic> in paired normal and tumor DNAs. Nine SNPs in <italic>HDAC9</italic> (<italic>rs801540</italic>, <italic>rs1178108</italic>, <italic>rs1178112</italic>, <italic>rs1726610</italic>, <italic>rs10243618</italic>, <italic>rs11764116</italic>, <italic>rs1178355</italic>, <italic>rs10269422</italic> and <italic>rs12540872</italic>) showed PAI in tumors. These data suggest that <italic>HDAC9</italic> variants may be selected for during cSCC tumorigenesis.</p> </abstract>