Molecular Genetic Investigation of Sporadic Renal Cell Carcinoma: Analysis of Allele Loss on Chromosome 3p

Choi, Jin Ho; Choi, Han Yong; Lee, Hyung Rae; Lee, Sung Won; Park, Kwan Hyun; Lee, Kyu Sung; Kim, Dae Sik; Chai, Soo Eung

Abstract

PURPOSE: Renal cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3, which suggests the presence of a tumor suppressor gene at this location. The aim of study was to investigate the role of tumor suppressor genes on the short arm of chromosome 3 in the mechanism of tumorigenesis in sporadic renal cell carcinoma. MATERIALS AND METHODS: The DNA from normal and tumor tissue from 48cases with renal cell carcinoma was analyzed for allele loss on chromosome 3p by polymerase chain reaction using microsatellite marker.
RESULTS
A total of 37 of 48 informative tumors(77%) showed loss of heteroxygosity(LOH) at one or more loci. Detailed analysis of the pattern of LOH on the chromosome 3p suggested that mutations of other genes in chromosome 3p13-p24, in addition to VHL gens in chromosome 3p25, are required for malignant tumor growth. There was the statistically significant correlation between the extent of LOH and cancer cell type(clear vs. others)(p=value 0.048, Fisher's exact test). A total of 26 of 37 clear cell types(70%)revealed LOH on chromosome 3p, but all of 11 non clear cell types including 2 granular cell types, 3 chromophobe types, 1 sarcomatoid cell type and 5 mixed cell types showed LOH. There was no correlation between LOH and other clinico-pathological factors including patients age, sex, symptom, tumor size, stage of disease and tumor cell grade.
CONCLUSIONS
Our data suggest that, in addition to VHL gene, at least one tumor suppressor gene for the genesis of sporadic remal cell carcinoma exists on the short arm of chromosome 3.