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Loss of Constitutional Heterozygosity in Colorectal Tumors from Patients with Familial Polyposis Coli and Those with Nonpolyposis Colorectal Carcinoma¹

Department of Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan [M. S., K. S., J. S. T. S.]; Department of Biochemistry, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113, Japan [M. O., C. S., M. M.]; The Research Center for Polyposis and Intestinal Disease, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113, Japan [T. Iw]; and Department of Cytogenetics, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113, Japan [T. Ik., A. T.]

Familial polyposis coli (FPC) is an autosomal dominant tumorigenic disorder, the major gene of which is mapped to chromosome 5q. We searched for a gene loss in colorectal tumors from FPC patients, as related to tumorigenesis by inactivation of tumor suppression genes, using restriction fragment length polymorphism analysis. The findings were compared with those in the case of nonpolyposis colorectal carcinomas (NPCC). We examined specimens from 39 FPC patients, including 21 adenocarcinomas and 49 adenomas, and 23 colorectal carcinomas from 22 NPCC patients. For this, we used 53 polymorphic DNA markers on all autosomes. Frequent loss of heterozygosity in colorectal carcinoma from FPC patients was observed on chromosomes 5 (24%), 14 (20%), 17 (31%), 18 (40%), and 22 (35%) and also on chromosomes 5 (32%), 14 (30%), 17 (27%), 18 (20%), and 22 (19%) in NPCC. Although loss of heterozygosity in adenoma from FPC patients was observed on nine chromosomes, the frequencies were less than 7%. As we fractionated tumors only macroscopically, actual frequencies of loss of heterozygosity are probably somewhat higher. However, these results do suggest that tumor suppression genes for colorectal carcinoma may locate on chromosomes 5, 14, 17, 18, and 22 and that they may play a critical role in carcinogenesis in both FPC and NPCC patients.

¹ This work was supported in part by Grants-in-Aid for Cancer Research 60010032, 60015072, 61010033, 61015078, 62010031, and 62015059 from the Ministry of Education, Science, and Culture, Japan, and by a Grant-in-Aid from the Fukuoka Cancer Society.

² To whom requests for reprints should be addressed.

Received 8/29/88. Revised 2/16/89. Accepted 4/13/89.

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