Methylation of the hMLH1, p16, and MDR1 genes in colorectal carcinoma: associations with clinicopathological features.
The methylation status of seven cancer-related genes was investigated in a series of 58 colorectal cancers, 18 of which showed the microsatellite instability (MSI+) phenotype. Methylation of the hMLH1, p16 and MDR1 genes was found in 23, 29 and 28% of tumors, respectively. None of the tumors showed methylation of the TS, ATM, PARP or p21 genes. Methylation of the hMLH1, p16 and MDR1 genes was more frequent and more concordant in MSI+ compared to MSI- tumors (P<0.001) and was also strongly associated with poor histological differentiation (P<0.001). There were trends for associations between methylation at one or more of these loci and proximal tumor location, advanced Dukes' stage and the presence of wild-type p53 (P=0.06 for each).
Shannon
B A
BA
Department of Surgery, University of Western Australia, WA 6009, Nedlands, Australia.
Iacopetta
B J
BJ
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005260:Female; D019450:Genes, MDR; D019942:Genes, p16; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D013940:Thymidylate Synthase; D011065:Poly(ADP-ribose) Polymerases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000070957:MutL Protein Homolog 1