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Mutations of APC, K-ras, and p53 Are Associated with Specific Chromosomal Aberrations in Colorectal Adenocarcinomas¹

Departments of Surgery and Molecular Oncology [A. L., R. J. C. S.], Human Genetics [N. R. P., K. G., M. S.], and Molecular and Cellular Pathology [N. M. K., F. A. C.], Biomedical Research Centre [G. S.], and Cancer Research UK, Molecular Pharmacology Unit, Biomedical Research Centre [C. R. W.], University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, United Kingdom

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.

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