Molecular genetic studies of colon cancer.

Molecular genetic studies of tumor-specific allele loss, originally associated primarily with research regarding childhood hereditary cancers such as retinoblastoma and Wilms' tumors, only lately have been recognized as a relatively fast and fruitful way of locating cancer genes on human chromosomes. To date, over 25 different cancers have been tied to a gene (or genes) on a specific chromosome when this method has been used. During the past year alone, this approach has permitted detection of three genes involved in either hereditary or sporadic colorectal cancers. These three genes, located on chromosomes 5q, 17p, and 18q, are believed to belong to the newly described tumor suppressor (or growth suppressor) gene class, whose effects are opposite those of activated cellular oncogenes, which promote uncontrolled cell growth. Present studies, however, have not shown losses of any of these tumor suppressor genes to be correlated with the presence of activated ras genes in colorectal adenomas or carcinomas. During progression from adenoma to carcinoma, ras gene mutations and 5q allelic deletions are likely to be earlier events, whereas allelic losses from chromosomes 18q and 17p seem to occur more often in advanced tumors. Involvement of the genes on 5q (FAP) and 18q (Lynch syndrome II) in hereditary colon cancer syndromes is supported by linkage studies, but their respective roles (as well as that of the gene on 17p) in familial and sporadic colorectal cancer remain to be precisely defined. Probable isolation of these three genes by molecular cloning within the next few years will help elucidate their specific biologic functions. It will also permit early detection, and thus prevention, of some familial colon cancers (such as FAP), and possibly allow DNA marker-based separation of different colon cancer subtypes of similar histologic appearance.