Clues to the Pathogenesis of Familial Colorectal Cancer
Abstract
A predisposition to colorectal cancer is shown to be linked to markers on chromosome 2 in some families. Molecular features of "familial" cancers were compared with those of sporadic colon cancers. Neither the familial nor sporadic cancers showed loss of heterozygosity for chromosome 2 markers, and the incidence of mutations in KRAS, P53, and APC was similar in the two groups of tumors. Most of the familial cancers, however, had widespread alterations in short repeated DNA sequences, suggesting that numerous replication errors had occurred during tumor development. Thirteen percent of sporadic cancers had identical abnormalities and these cancers shared biologic properties with the familial cases. These data suggest a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes.
Get full access to this article
View all available purchase options and get full access to this article.
References
BOS, J.L., PREVALENCE OF RAS GENE-MUTATIONS IN HUMAN COLORECTAL CANCERS, NATURE 327: 293 (1987).
CAMPO, E, LOSS OF HETEROZYGOSITY OF P53-GENE AND P53-PROTEIN EXPRESSION IN HUMAN COLORECTAL CARCINOMAS, CANCER RESEARCH 51: 4436 (1991).
CASKEY, C.T., TRIPLET REPEAT MUTATIONS IN HUMAN-DISEASE, SCIENCE 256: 784 (1992).
CLEAVER, J.E., DEFECTIVE REPAIR REPLICATION OF DNA IN XERODERMA PIGMENTOSUM, NATURE 218: 652 (1968).
DUNLOP, M.G., SCREENING FOR LARGE-BOWEL NEOPLASMS IN INDIVIDUALS WITH A FAMILY HISTORY OF COLORECTAL-CANCER, BRITISH JOURNAL OF SURGERY 79: 488 (1992).
FEARON, E.R., A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS, CELL 61: 759 (1990).
FORRESTER, K, DETECTION OF HIGH-INCIDENCE OF K-RAS ONCOGENES DURING HUMAN-COLON TUMORIGENESIS, NATURE 327: 298 (1987).
GERMAN, J, BLOOMS SYNDROME .12. REPORT FROM THE REGISTRY FOR 1987, CLINICAL GENETICS 35: 57 (1989).
GRODEN, J, IDENTIFICATION AND CHARACTERIZATION OF THE FAMILIAL ADENOMATOUS POLYPOSIS-COLI GENE, CELL 66: 589 (1991).
HOULSTON, R.S., DOMINANT GENES FOR COLORECTAL-CANCER ARE NOT RARE, ANNALS OF HUMAN GENETICS 56: 99 (1992).
JOSLYN, G, IDENTIFICATION OF DELETION MUTATIONS AND 3 NEW GENES AT THE FAMILIAL POLYPOSIS LOCUS, CELL 66: 601 (1991).
KINZLER, K.W., IDENTIFICATION OF FAP LOCUS GENES FROM CHROMOSOME-5Q21, SCIENCE 253: 661 (1991).
KNUDSON, A.G., HEREDITARY CANCER, ONCOGENES, AND ANTIONCOGENES, CANCER RESEARCH 45: 1437 (1985).
KOURI, M, DIPLOID PREDOMINANCE IN HEREDITARY NONPOLYPOSIS COLORECTAL-CARCINOMA EVALUATED BY FLOW-CYTOMETRY, CANCER 65: 1825 (1990).
LANDEGREN, U, A LIGASE-MEDIATED GENE DETECTION TECHNIQUE, SCIENCE 241: 1077 (1988).
Li, S.H., Genomics 16: 572 (1993).
LYNCH, H.T., HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER (LYNCH SYNDROME-I AND SYNDROME-II) - GENETICS, PATHOLOGY, NATURAL-HISTORY, AND CANCER CONTROL .1., CANCER GENETICS AND CYTOGENETICS 53: 143 (1991).
LYNCH, P.M., HEREDITARY PROXIMAL COLONIC CANCER, DISEASES OF THE COLON & RECTUM 20: 661 (1977).
McKinnon, P. J., Human Genetics 75: 197 (1987).
MECKLIN, J.P., TUMOR SPECTRUM IN CANCER FAMILY SYNDROME (HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER), CANCER 68: 1109 (1991).
MECKLIN, J.P., CLINICAL-FEATURES OF COLORECTAL-CARCINOMA IN CANCER FAMILY SYNDROME, DISEASES OF THE COLON & RECTUM 29: 160 (1986).
NISHISHO, I, MUTATIONS OF CHROMOSOME-5Q21 GENES IN FAP AND COLORECTAL-CANCER PATIENTS, SCIENCE 253: 665 (1991).
PEINADO, M.A., ISOLATION AND CHARACTERIZATION OF ALLELIC LOSSES AND GAINS IN COLORECTAL TUMORS BY ARBITRARILY PRIMED POLYMERASE CHAIN-REACTION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 10065 (1992).
PELTOMAKI, P, GENETIC-MAPPING OF A LOCUS PREDISPOSING TO HUMAN COLORECTAL-CANCER, SCIENCE 260: 810 (1993).
Perucho, M., paper presented at the International Symposium on Human Oncogenes, Madrid, Spain, 8 April (1992).
POWELL, S.M., APC MUTATIONS OCCUR EARLY DURING COLORECTAL TUMORIGENESIS, NATURE 359: 235 (1992).
POWELL, S.M., unpublished data.
RODRIGUES, N.R., P53 MUTATIONS IN COLORECTAL-CANCER, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 7555 (1990).
SIDRANSKY, D, IDENTIFICATION OF RAS ONCOGENE MUTATIONS IN THE STOOL OF PATIENTS WITH CURABLE COLORECTAL TUMORS, SCIENCE 256: 102 (1992).
STANBRIDGE, E.J., HUMAN TUMOR SUPPRESSOR GENES, ANNUAL REVIEW OF GENETICS 24: 615 (1990).
van den Berg, F. M., Journal of Pathology 157: 193 (1989).
VASEN, H. F. A., DISEASES OF THE COLON & RECTUM 34: 424 (1991).
VOGELSTEIN, B, GENETIC ALTERATIONS DURING COLORECTAL-TUMOR DEVELOPMENT, NEW ENGLAND JOURNAL OF MEDICINE 319: 525 (1988).
VOGELSTEIN, B, ALLELOTYPE OF COLORECTAL CARCINOMAS, SCIENCE 244: 207 (1989).
VOGELSTEIN, B, SCIENCE 244: 217 (1989).
WEBER, J.L., ABUNDANT CLASS OF HUMAN DNA POLYMORPHISMS WHICH CAN BE TYPED USING THE POLYMERASE CHAIN-REACTION, AMERICAN JOURNAL OF HUMAN GENETICS 44: 388 (1989).
WEINBERG, R.A., TUMOR SUPPRESSOR GENES, SCIENCE 254: 1138 (1991).
WEISSENBACH, J, A 2ND-GENERATION LINKAGE MAP OF THE HUMAN GENOME, NATURE 359: 794 (1992).
(0)eLetters
eLetters is an online forum for ongoing peer review. Submission of eLetters are open to all. eLetters are not edited, proofread, or indexed. Please read our Terms of Service before submitting your own eLetter.
Log In to Submit a ResponseNo eLetters have been published for this article yet.
Information & Authors
Information
Published In
Science
Volume 260 | Issue 5109
7 May 1993
7 May 1993
Copyright
© 1993.
Submission history
Published in print: 7 May 1993
Authors
Metrics & Citations
Metrics
Article Usage
Altmetrics
Citations
Export citation
Select the format you want to export the citation of this publication.
Cited by
Loading...
View Options
Check Access
Log in to view the full text
AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.
- Become a AAAS Member
- Activate your AAAS ID
- Purchase Access to Other Journals in the Science Family
- Account Help
Log in via OpenAthens.
Log in via Shibboleth.
More options
Purchase digital access to this article
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
View options
PDF format
Download this article as a PDF file
Download PDF