Objective: It is demonstrated that KRAS2, functioning as an oncogene, plays a critical role in carcinogenesis. However, some studies suggest that the wild type KRAS2, located in the region of 12p12.1, takes its effect as a tumor suppressor gene. This study, therefore, is aimed to investigate the loss of heterozygosity (LOH) on chromosome 12p12-13 region in 10 human colon carcinomas.
Methods: LOH analysis of the 12p12-13 region was performed by PCR, using 11 microsatellite markers in 12p12-13 region. The relationships between LOH for each marker and clinical pathologic factors were evaluated.
Results: LOH in at least one of the loci in 12p12-13 region was detected in 30% (3/10) of adjacent tissues; the highest frequency of LOH was identified at the locus of D12S1034 in 28.57% (2/7) of adjacent tissues. 60% (6/10) carcinoma tissues were found to have LOH in at least one locus in the same region; the most frequent LOH was found at the loci of D12S1034 and D12S1591, both about 42.86% (3/7). Among all samples, 3 cases were noted to have LOH in both adjacent and tumor tissues, and 3 cases were shown to have LOH only in tumor tissues. Occurrence of LOH was not correlated with sex, age, tumor size and lymph node metastasis.
Conclusion: Allelic loss on 12p12-13 region would influence the KRAS2 expression by reducing the gene-dosage in colon carcinogenesis.