Abstract 1184: Prognostic significance of genetic alterations detected by high-density single nucleotide polymorphism (SNP) array in gastrointestinal cancer

Abstract

Abstract (Background and aims) We sought to identify specific gene that would be useful for predicting the prognosis of gastrointestinal cancer by the use of high-density single nucleotide polymorphism (SNP) array. (Materials and Methods) We performed genome-wide analysis of 35 colorectal cancer (CC), 34 gastric cancer (GC), 17 Liver cancer and 26 pancreatic cancer cell lines using Affymetrix GeneChip Human mapping 100K Set. These analyses showed 10 remarkably recurrent homozygous deleted regions. These 10 regions were fine and contained only 1-2 genes, respectively. So, we chose 10 genes from these 10 regions and performed loss of heterozygosity (LOH) analyses using 64 CC (38 men and 26 women; mean age; 65.8±10.4 yr) and 42 GC (29 men and 13 women; mean age; 64.8±11.7 yr) tissues. For precise evaluation of LOH, laser capture microdissection was performed, minimizing the chance of contamination by non-tumor tissues. These 10 genes included the genes that have been not reported to be deleted in cancer besides FHIT and CDKN2A gene, which were known to be deleted in several cancers. (Results) LOH of these 10 genes was detected in 35.5 %-74.6 % of CC and 39.0 %-67.5 % of GC tissues, respectively. We divided CC and GC into two groups (LOH-H; showing LOH of 5 genes or more, LOH-L; showing LOH of less than 5 genes), respectively. In CC, LOH-H showed a significant positive association with lymphatic invasion and lymph nodes metastasis (p = 0.007 and 0.04). On the other hand, LOH-H showed a significant positive association with lymph nodes metastasis (p = 0.019) in GC. The prognosis of the patients with LOH-L was significantly better than that of those with LOH-H in all CC cases (p = 0.038), while subgroup analysis showed that the prognosis of CC patients with LOH-L tended to be better than that of those with LOH-H in stage I + II CC cases (p = 0.057). Similarly, the prognosis of the patients with LOH-L was significantly better than that of those with LOH-H in all GC cases (p = 0.048). Subgroup analysis showed that the prognosis of the patients with LOH-L was also significantly better than that of those with LOH-H in stage I + II GC cases (p = 0.037). Multivariate analyses showed that stage and the LOH status were independent significant prognostic factors in CC and size and the LOH status were independent prognostic factors in GC. (Conclusion) LOH of these 10 genes might be a novel molecular signature of CC and GC with malignant phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1184.