The impact of a high-frequency microsatellite instability phenotype on the tumor location-related genetic differences in colorectal cancer

Zhao Y, Oki E, Ando K, Morita M, Kakeji Y, Maehara Y.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Abstract
The purpose of this study was to evaluate the genetic background of colorectal cancer according to the tumor site, and to investigate the impact of the genetic features regarding the lesion location of colorectal cancer. Microsatellite instability (MSI), DNA index, and the mutation and loss of heterozygosity of the TP53 gene were systemically examined in 180 Japanese colorectal cancer cases. The correlation between these genetic features and clinicopathologic factors was analyzed. A logistic regression was undertaken to analyze the association between genetic features and tumor locations. The data demonstrated location-related genetic differences in colorectal cancer. The proximal subset was distinct in patterns of genomic instability and TP53 gene defects. The genetic features of distal colon cancers paralleled those of rectal cancers. Intriguingly, a multivariate analysis implicated MSI as the only factor significantly associated with tumor location. When MSI tumors were excluded, the statistical association between tumor location and alternations in the DNA index and TP53 vanished. The location-related differences of colorectal cancer were derived from the unequal distribution of the MSI tumors. On the other hand, the microsatellite stable colorectal cancers were genetically homogeneous regardless of the tumor location. Therefore, instead of tumor location, microsatellite status should be a major focus for the study of colorectal cancers in the future. 辽宁省肿瘤医院胃科赵岩

PMID: 20082848