GENOME-WIDE ANALYSIS OF LOSS HETEROZYGOSITY AND DISCOVERY OF NOVEL TUMOR SUPPRESSOR GENES IN GASTRIC CANCER

Abstract

Gastric cancer is the second leading cause of cancer death worldwide. Gastric cancers often undergo loss of heterozygosity (LOH), which is a common mechanism resulting in the inactivation of tumor suppressor genes (TSGs). Therefore, regions that are frequently and independently subject to LOH often harbor TSGs. However, patterns of LOH across multiple gastric tumors have yet to be extensively studied by the most thorough and sensitive method currently available: high-density single-nucleotide polymorphism (SNP) arrays. We report the results of genome-wide assessments of LOH, and copy number alterations in gastric tumors, each with matched non-malignant DNA. Analysis of regions that frequently undergo LOH in these tumors implicates TSGs already known to contribute to gastric carcinogenesis; these include TP53 (80%), CDKN2A (67%) and APC (53%). This analysis also implicates several candidate TSGs that, to our knowledge, have not been previously linked gastric carcinogenesis. These genes include PTPRD and DOCK8 on chromosome 9p.