Mismatch repair, p53 and chromosomal aberrations in primary colorectal carcinomas.
Colorectal carcinoma progresses via at least two genetic pathways. Microsatellite instability, due to defective mismatch repair genes, characterizes one pathway and gross chromosomal instability another. The involvement of p53 and mismatch repair gene abnormalities within these pathways has not been fully explored. We aimed to investigate the relationships of p53 and mismatch repair gene defects on gross chromosomal aberrations detected by comparative genomic hybridization in 49 colorectal carcinomas. Tumours demonstrating loss of expression for hMLH1 or hMSH2 proteins demonstrated a highly significant attenuation in the number of gross chromosomal aberrations (p = 0.007) and were less likely to show p53 overexpression (p = 0.02). Within the mismatch repair normal tumours, p53 status did not affect the total number of chromosomal aberrations but p53 overexpression was significantly associated with a higher frequency of amplifications at 8q22-ter and at 13q21-22. Colorectal cancer demonstrates distinct molecular phenotypes and should be sub-classified accordingly.
Mehigan
Brian J
BJ
Postgraduate Medical Institute of the University of Hull and Hull York Medical School, University of Hull, UK.
Ashman
James N E
JN
Baker
Richard P
RP
Macdonald
Alastair
A
Greenman
John
J
Monson
John R T
JR
Cawkwell
Lynn
L
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D018450:Disease Progression; D016158:Genes, p53; D006801:Humans; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D016159:Tumor Suppressor Protein p53
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C088996:PMS1 protein, human; D016159:Tumor Suppressor Protein p53; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins