Genomic Imprinting Of IGF2 Gene In Lung Cancer

Background and object: Genomic imprinting is a parentalorigin-specific chromosomal modification that causes differentalexpression of maternal and paternal alleles of a gene. It is a non-Mendelianinherited epigenetic form of gene regulation that results in monoallelicexpression. Accumulating evidence suggests that deregulation of imprintedgenes, including loss of imprinting (LOI), plays a role in oncogenesis. LOIof the insulin-like growth factor 2 gene (IGF2) is found in a number oftumors, suggesting that LOI of IGF2 may play an important role intumorigenesis. In the present study, we investigated allelic expression ofIGF2 gene in human lung cancer as well as in matched normal lung tissiuein order to study the imprinting status and expression level of IGF2 andprovide a clue for the mechanism of carcinogenesis of lung cancer. Methods: We compared the imprinting status and expression level ofIGF2 in both lung cancer samples and the matched normal tissues.Genomic DNA from 32 lung cancer patients was amplified by polymerasechain reaction (PCR) and screened for heterozygosity at IGF2 usingrestriction endonuclease Apaâ… . If heterozygous, polyadenylated RNAwas isolated and reversed-transcribed into cDNA. CDNA then wasamplified by PCR and the products were digested with the same restrictionenzymes to evaluate lung cancer expression of IGF2. Results: Twelve of 32 patients (37.5%) studied were informative.Lung cancer tissue from 10 of the 12 informative patients(83.3%) exhibitLOI of IGF2; furthermore, the matched normal tissues from 4 of these 10patients also shows weak biallelic expression of IGF2. The tendency ofLOI of IGF2 was biased toward poorly and moderately differentiated ratherthan well-differentiated cancer. IGF2 was overexpressed in lung cancertissues which was significantly higher than those of the matched normaltissues. Conclusion: The findings indicated that independent deregulationtook place in imprinted genes and suggested that aberrant imprinting andoverexpression of IGF2 play an important role in carcinogenesis of lungcancer. LOI of IGF2 may be a prophase manifestation of lung cancer.