Imprinting abnormalities may contribute to tumorigenesis by either activation of a transcriptionally repressed allele or inactivation of a normally expressed allele. Disruption of an imprinting control center could also cause aberrant expression of multiple imprinted proto oncogenes and/or tumor suppressor genes, because expression of imprinted genes is often coordinately regulated within a chromosomal domain.
I examined the expression patterns of imprinted genes in various cancers. For example, loss of imprinting of IGF2 and PEG1/MEST were observed in 47% and 85% of lung adenocarcinomas respectively, indicating that aberrant imprinting of IGF2 and PEG1/MEST may be involved in the development of lung adenocarcinoma. Another example is that PEG3 was epigenetically down-regulated in a considerable number of glioma cells, suggesting that PEG3 is a component of the molecular pathway for glioma carcinogenesis. Thus, the abnormal epigenetic modification of imprinted genes is a common event in carcinogenesis.
Real-time PCR has been used to develop a novel high-throughput method for the determination and quantitation of single-nucleotide polymorphism (SNP) allele frequency in DNA samples. In order to examine a large number of cases, I developed an alternative high-throughput method for the analysis of imprinting disorders using SNPs. For example, the kinetic PCR method for quantification of PEG1/MEST gene expression and allele frequency produced results similar to that of conventional PCR-restriction fragment length polymorphism analysis.