Analysis of Genomic Imprinting of Insulin-Like Growth Factor 2 in Colorectal Cancer

Abstract

Genomic imprinting of insulin-like growth factor 2 (IGF2) has been shown to play an important role in the development of Wilms’ tumor and adult cancers including lung and esophageal cancer. Although IGF2 has been reported to be overexpressed in colorectal cancer, the status of this gene has not been fully elucidated. To clarify genomic imprinting of IGF2 in colorectal cancer, we examined loss of imprinting (LOI) and loss of heterozygosity (LOH) in surgically resected tissues by utilizing Apa1 polymorphism. Of 46 patients with colorectal cancer, 2 exhibited (2/15, 13%) LOH among 15 patients who were heterozygous for IGF2 DNA in nontumorous tissues. Four (4/12, 33%) patients showed LOI of IGF2 gene among informative patients. In these patients, the reverse transcription polymerase chain reaction and immunohistochemistry revealed that IGF2 mRNA is overexpressed in tumorous tissues, compared to nontumorous tissues. Of 15 patients in whom IGF2 was immunohistochemically more highly expressed in tumorous than in normal tissues, there were 2 with LOH and 4 with LOI. The results of the present study suggest that LOI of IGF2 plays an important role in the carcinogenesis of colorectal cancer.