Mutations of APC, K-ras, and p53 are associated with specific chromosomal aberrations in colorectal adenocarcinomas

• Published in: Cancer research (Chicago, Ill.) Ill.), 2003-08, Vol.63 (15), p.4656-4661
• Main Authors: LESLIE, Amy, PRATT, Norman R, GILLESPIE, Karen, SALES, Mark, KERNOHAN, Neil M, SMITH, Gillian, WOLF, C. Roland, CAREY, Francis A, STEELE, Robert J. C
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Aged, 80 and over; APC gene; Biological and medical sciences; Carrier Proteins; Chromosome Aberrations; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; DNA-Binding Proteins; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes, APC; Genes, p53; Genes, ras; Genotype; Humans; Immunohistochemistry; K-ras gene; Male; Medical sciences; Middle Aged; Mutation; MutL Protein Homolog 1; MutS Homolog 2 Protein; Neoplasm Proteins - metabolism; Nuclear Proteins; Proto-Oncogene Proteins - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0008-5472; 1538-7445

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.