Colon cancer claims the lives of more than 65,000 people each year in the United States, second only to lung cancer. Surgery remains the only effective means of treatment, and even this is usually only effective when the cancer is discovered early. Patients with an inherited predisposition for developing numerous premalignant polyps (familial polyposis) are at nearly 100% risk of colon cancer by age 40, and early scrutiny of such patients often leads to prophylactic surgery. However, the great majority of patients who will present with colon cancer do not have a prehistory of polyposis that might lead to early detection. Recently, some oncogenes (ras) and candidate tumor suppressor genes (p53, DCC, MCC) have been implicated in playing a role at various stages of premalignant and malignant progression in the colon adenoma-carcinoma sequence. Therefore, it appears that several, if not many, genes can contribute to progression. The genes that have been implicated thus far have been linked to cytogenetically-observable abnormalities or to fortuitously located restriction fragment length polymorphisms (RFLPs). In order to directly investigate the major alterations in gene expression in polyposis and colon carcinoma, cDNA libraries from matched tumor/normal tissues were constructed. Subtractive cDNA libraries enriched for either tumor-specific or normal-specific cDNAs were then constructed and used to isolate clones differentially expressed in tumor and normal tissues. A number of such clones have been isolated. Some of these correspond to already identified genes whose possible role in colon cancer progression has not been previously suspected (e.g., collagen type VI, laminin-binding protein), while other clones do not correspond to any sequences thus far deposited in various sequence databases. One such clone, IH12, is growth-regulated and is also found to be overexpressed in breast carcinoma.
