1. Mutations of APC, K-ras, and p53 are associated with specific chromosomal aberrations in colorectal adenocarcinomas
- Author
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Amy, Leslie, Norman R, Pratt, Karen, Gillespie, Mark, Sales, Neil M, Kernohan, Gillian, Smith, C Roland, Wolf, Francis A, Carey, and Robert J C, Steele
- Subjects
Aged, 80 and over ,Chromosome Aberrations ,Male ,Genes, APC ,Genotype ,Nuclear Proteins ,Adenocarcinoma ,Middle Aged ,Genes, p53 ,Immunohistochemistry ,Neoplasm Proteins ,DNA-Binding Proteins ,Genes, ras ,MutS Homolog 2 Protein ,Proto-Oncogene Proteins ,Mutation ,Humans ,Female ,Carrier Proteins ,Colorectal Neoplasms ,MutL Protein Homolog 1 ,Adaptor Proteins, Signal Transducing ,Aged - 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.
- Published
- 2003