Published in Cancer Detection and Prevention 1995; 19(6):512-517.

Sampling Method as a Key Factor in Identifying K-ras Oncogene Mutations in Preneoplastic Colorectal Lesions

Ze'ev Ronai, Ph.D.a, Toshinari Minamoto, M.D.b, Ross Butler, M.D.c, Martin Tobi, M.D.d, Feng-Qui Luo, B.S.a, Edith Zang, Ph.D.a, Hiroyasu Esumi, M.D.b, and Takashi Sugimura, M.D.b

a Molecular Carcinogenesis Program, American Health Foundation, Valhalla, NY; b National Cancer Center Research Institute, Tokyo, Japan; c astroenterology, Women's and Children's Hospital, North Adelaide, South Australia; and d Department of Medicine, Wayne State University, Detroit, MI

Address all correspondence and reprint requests to: Z. Ronai, Ph.D., American Health Foundation, Molecular Carcinogenesis Program, I Dana Rd., Valhalla, NY 10595.

ABSTRACT: The development of sensitive polymerase chain reaction (PCR)-based techniques in recent years has enabled us to verify the possible presence of mutated oncogenes and tumor suppressor genes in stages preceding tumor formation. Early detection of mutants serves as a powerful tool for detecting exposure to carcinogens and can assist in diagnosis. In studies performed in the past few years, we have identified mutant ras alleles in preneoplastic samples of patients with and without colorectal cancer. Our studies have shown (i) that mutant ras alleles are present at low incidence in normal appearing tissues of patients with colorectal cancer. Such mutations are also found in colonic effluents of patients at risk for developing this tumor type; and (ii) that the method of sampling is critical to ensure true representation of the entire colonic mucosa. The implications of identifying ras mutations in patients without evidence for neoplasms are discussed.

KEY WORDS: ras mutation, early detection, colon cancer.