Molecular Analysis of the Retinoblastoma (Rb) Gene in Human Colorectal Carcinomas
We have examined the structure and expression of the Rb gene on chromosome 13 in matched pairs of normal and malignant colonic tissues from 68 patients. Northern blots showed a normal size 4.7 kb transcript in the 33 normal mucosal tissues and 38 colorectal carcinomas examined. However, increased expression of the Rb gene (2-5 fold) was detected in approximately 70% of colorectal carcinomas relative to normal colonic mucosa. The remaining malignant tissues showed an equal level of Rb specific RNA as compared to normal colonic mucosa and none showed a decrease in hybridization signal. Southern blot analysis of DNA from 45 colorectal carcinomas showed an increase in hydridization intensity (at least two fold) in 20 tumors in comparison to normal mucosa. These results coupled with previous reports of nonrandom chromosome 13 gains in approximately 50% of colorectal carcinomas suggest that an increase in Rb gene copy number occurs frequently in these tumors. Southern blot analysis also shows that none of the colorectal cancers examined had allelic loss at the Rb locus. These results suggest that the Rb gene is not lost or transcriptionally inactivated in colorectal cancers.
KeywordsColorectal Carcinoma Familial Adenomatous Polyposis Lynch Syndrome Familial Adenomatous Polyposis Patient Hybridization Intensity
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- Boman BM (1988) Biomolecular genetics of cancer. In: Lynch T and Hirayama T (ed) Genetic Epidemiology of Cancer. CRC Press, Inc. Boca Raton, FL, pp 343–349Google Scholar
- Deschner EE, Lipkin M (1978) Proliferation and differentiation of Gastrointestinal Cells in Health and Disease. In: Lipkin M and Good RA (ed) Gastrointestional Tract Cancer. Plenum Publishing Corp., New York, NYGoogle Scholar
- Li FP (1988) Cancer families: Human models of susceptibility to neoplasia-The Richard and Hinda Rosenthal Foundation Award Lecture. Cancer 48:5381–5386Google Scholar
- Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: A laboratory manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, New YorkGoogle Scholar
- Toguchida J, Ishizaki K, Sasaki MS, Ikenaga M, Sugimoto M, Kotoura Y, Yamamuro T (1988) Chromosomal reorganization for the expression of recessive mutation of retinoblastoma susceptibility gene in the development of osteosarcoma. Cancer 48:3939–3943Google Scholar
- Yokota J, Akiyama T, Fung Y-KT, Benedict WF, Namba Y, Hanaoka M, Wada M, Terasaki T, Shimosato Y, Sugimura T, Terada M (1988) Altered expression of the retinoblastoma (Rb) gene in small-cellGoogle Scholar