Abstract 28: Resequence-analysis of 166kb KITLG region in eamilial testicular germ cell tumors

Abstract

Abstract Recent genome-wide association studies (GWAS) have identified multiple loci associated with testicular germ cell tumor (TGCT) risk, particularly in KITLG on chromosome 12q22, which has the strongest per-allele odds ratio in cancer GWAS to date. KITLG, also known as stem cell factor or Steel, encodes the ligand for the membrane receptor tyrosine kinase, c-KIT. It is notable that mutations in the KIT/KITLG system have been implicated in both testicular cancer development and infertility, both of which are established TGCT risk factors. Therefore, a comprehensive cataloguing of variants around the region is essential for further functional studies. We defined a 166kbps region (chromosome 12: 87371132-87537273) around KITLG, based on linkage disequilibrium patterns and tag analysis using HapMap III CEU and the 1000 genome CEU low-coverage pilot data (July 2010 release). No obvious recombination hotspot was observed within a 1Mb region centered on KITLG. Our study sample set included 10 parent-son trios, of which 6 trios contained 2 familial TGCT cases, 51 familial TGCT cases and 36 sporadic bilateral cases, totaling 117 individuals, all from the National Cancer Institute's Familial Testicular Cancer Study (FTCS). We have catalogued common and rare KITLG variants using deep coverage in next-generation sequencing and also identified haplotypes possibly enriched in familial cases in contrast to normal controls. These study results will facilitate further functional elucidation of TGCT susceptibility loci within this genomic region. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 28. doi:10.1158/1538-7445.AM2011-28