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 instability (MSI)-positive sporadic colorectal cancers, we have investigated alteration 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. H19 expression was not detected in 24% of informative cancers. SNRPN and NDN retained monoallelic expression in all the cancers examined. These findings indicate no simultaneous disruption 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. Moreover, MSI-positive colorectal cancers exhibit LOI of IGF2 with a high frequency compared to MSI-negative cancers (P=0.013). These observations, consistent with a previous report, establish an association between LOI of IGF2 and MSI in colorectal cancers and provide insight into susceptibility of tumor development.
Nishihara
S
S
Core Research for Evolutional Science and Technology (CREST) Program, Department of Molecular and Cell Genetics, School of Life Sciences, Tottori 683-8503, Japan.
Hayashida
T
T
Mitsuya
K
K
Schulz
T C
TC
Ikeguchi
M
M
Kaibara
N
N
Oshimura
M
M
D000483:Alleles; D001324:Autoantigens / Q000235:genetics; D015415:Biomarkers; D015179:Colorectal Neoplasms / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins
D001324:Autoantigens; D015415:Biomarkers; C408145:IGF2-AS lncRNA, human; D009363:Neoplasm Proteins; D011506:Proteins; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; C103637:mesoderm specific transcript protein; D055517:snRNP Core Proteins