Multipoint imprinting analysis in sporadic colorectal cancers with and without microsatellite instability

Disrupted imprinting is implicated in certain tumorigenesis. Since aberrant methylation has been described for a majority of microsatellite instabilit y (MSI)-positive sporadic colorectal cancers, we have investigated alterati on to the imprinting in 55 sporadic colorectal cancers with or without MSI. Loss of imprinting (LOI) of IGF2 and PEG1/MEST was observed in 42% and 35% of informative cancers, respectively. 1119 expression was not detected in 24% of informative cancers. SNRPN and NDN retained monoallelic expression i n all the cancers examined. These findings indicate no simultaneous disrupt ion of the imprinted genes. LOI of IGF2 and PEG1/MEST was also observed in colorectal mucosa from almost all the patients with LOI in tumor tissue. Mo reover, MSI-positive colorectal cancers exhibit LOI of IGF2 with a high fre quency compared to MSI-negative cancers (P=0.013). These observations, cons istent with a previous report, establish an association between LOI of IGF2 and MSI in colorectal cancers and provide insight into susceptibility of t umor development.