Specific patterns of chromosomal abnormalities are associated with RER status in sporadic colorectal cancer.
Current opinion of the genetic events driving colorectal tumourigenesis focuses on genomic instability. At least two apparently independent mechanisms are recognized, microsatellite instability and chromosomal instability. The genetic defects underlying each type of instability are only partially understood and controversy remains as to the role of p53 in the generation of chromosomal defects in colorectal cancer. This study sought to clarify the relationships between chromosomal abnormalities and defects of both p53 and mismatch repair. Extensive chromosomal analysis was undertaken, using flow cytometry and comparative genomic hybridization, of a series of sporadic colorectal cancers which had been grown to early passage as subcutaneous xenografts in SCID mice. Overall levels of chromosomal defects were observed to be low in RER+ cancers compared with RER- and distinctive patterns of chromosomal anomalies were found to be associated with both the RER+ and RER- phenotype. No particular level or pattern of chromosomal anomalies appeared to be associated with p53 status, supporting recent observations that abnormal p53 function is not sufficient to cause chromosomal anomalies in colorectal tumours.
Curtis
L J
LJ
Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. ljcurtis32@hotmail.com
Georgiades
I B
IB
White
S
S
Bird
C C
CC
Harrison
D J
DJ
Wyllie
A H
AH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D016158:Genes, p53; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D009693:Nucleic Acid Hybridization; D011003:Ploidies; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53