title: Mutations of APC, K-ras, and p53 are associated with specific chromosomal aberrations in colorectal adenocarcinomas.
abstract: 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.
authors.affiliation: Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK. a.leslie@dundee.ac.uk
authors.forename: Amy
authors.initials: A
authors.lastname: Leslie
authors.forename: Norman R
authors.initials: NR
authors.lastname: Pratt
authors.forename: Karen
authors.initials: K
authors.lastname: Gillespie
authors.forename: Mark
authors.initials: M
authors.lastname: Sales
authors.forename: Neil M
authors.initials: NM
authors.lastname: Kernohan
authors.forename: Gillian
authors.initials: G
authors.lastname: Smith
authors.forename: C Roland
authors.initials: CR
authors.lastname: Wolf
authors.forename: Francis A
authors.initials: FA
authors.lastname: Carey
authors.forename: Robert J C
authors.initials: RJ
authors.lastname: Steele
mesh_terms: 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
chemical_list: 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