Mutations of APC, K-ras, and p53 are associated with specific chromosomal aberrations in colorectal adenocarcinomas.
It is widely accepted that both large-scale chromosomal abnormalities and mutation of specific genes, such as APC, K-ras, and/or p53, occur in the majority of colorectal adenocarcinomas. Whether or not a relationship exists between these different forms of genetic abnormalities was previously unknown. Using comparative genomic hybridization and mutational analysis of APC, K-ras, and p53 to evaluate 50 colorectal adenocarcinomas, we have shown that mutation of p53 is significantly associated with gain of 20q, 13q, and 8q and loss of 18q (P = 0.000, 0.02, 0.044, and 0.001, respectively). Conversely, APC mutation did not associate with any of the above-mentioned aberrations but did associate significantly with gain of 7p (P = 0.01). Gain of chromosomal arm 12p, although a less common aberration, was significantly associated with K-ras mutation (P = 0.011). The associations we have described should refine the search for candidate genes underlying chromosomal aberrations and assist in the definition of distinct pathways in colorectal tumorigenesis.
Leslie
Amy
A
Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK. a.leslie@dundee.ac.uk
Pratt
Norman R
NR
Gillespie
Karen
K
Sales
Mark
M
Kernohan
Neil M
NM
Smith
Gillian
G
Wolf
C Roland
CR
Carey
Francis A
FA
Steele
Robert J C
RJ
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D005260:Female; D017491:Genes, APC; D016158:Genes, p53; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein