Abstract
PURPOSE: Genetic tests are available for familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. The goal of this review was to develop an algorithm for application of molecular diagnostic techniques to the management of hereditary colorectal carcinoma and to familiarize the clinician with the vocabulary of molecular genetic testing for hereditary colorectal carcinoma. METHODS: Studies examining the clinical use of genetic testing for hereditary colorectal carcinoma syndromes are evaluated. Recent advances in molecular genetic technology are reviewed, and clinical management as practiced here and elsewhere is outlined. RESULTS: This review is a guide to the most reliable molecular diagnostic techniques. Three key questions are answered: who, when, and how to test. CONCLUSIONS: When integrated with existing testing protocols for colorectal carcinoma and when applied with appropriate caveats, particularly regarding interpretation of negative results, genetic testing can result in improved management of patients and families.
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References
Wong N, Lasko D, Rabelo R, Pinsky L, Gordon PH, Foulkes W. Genetic counseling and interpretation of genetic tests in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. Dis Colon Rectum (in press).
Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin 1998;48:6–29.
McLaughlin JR, Fields AL, Levy I,et al. National Cancer Institute of Canada: Canadian Cancer Statistics, 1999. Toronto: National Cancer Institute of Canada, 1999.
Foulkes WD. A tale of four syndromes: familial adenomatous polyposis, Gardner syndrome, attenuated APC and Turcot syndrome. Q J Med 1995;88:853–63.
Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996;87:159–70.
White, RL. Tumor suppressing pathways. Cell 1998;92:591–2.
Groden J, Thliveris A, Samowitz W,et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991;66:589–600.
Nishisho I, Nakamura Y, Miyoshi Y,et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991;253:665–9.
Heyer J, Yang K, Lipkin M, Edelmann W, Kucherlapati R. Mouse models for colorectal cancer. Oncogene 1999;18:5325–33.
Laken SJ, Petersen GM, Gruber SB,et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract inAPC. Nat Genet 1997;17:79–83.
Woodage T, King SM, Wacholder S,et al. The APC I1307K allele and cancer risk in a community-based study of Ashkenazi Jews. Nat Genet 1998;20:62–5.
Redston M, Nathoson KL, Yuan ZQ,et al. The APC I1307K allele and breast cancer risk. Nat Genet 1998;20:13–4
Bulow S. Clinical features in familial polyposis coli: results of the Danish Polyposis Register. Dis Colon Rectum 1986;29:102–7.
Lynch HT, Smyrk T, Lynch JF. Overview of natural history, pathology, molecular genetics and management of HNPCC (Lynch Syndrome). Int J Cancer 1996;69:38–43.
Thorson AG, Knezetic JA, Lynch HT. A century of progress in hereditary nonpolyposis colorectal cancer (Lynch Syndrome). Dis Colon Rectum 1999;42:1–9.
Vasen HF, Watson P, Mecklin J-P, Lynch HT. New clinical criteria for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 1999;116:1453–6.
Wijnen J, Vasen H, Khan M,et al. Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. N Engl J Med 1998;339:511–8.
Modrich P, Lahue R. Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Ann Rev Biochem 1996;65:101–33.
Fishel R, Lescoe MK, Rao MR,et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 1993;75:1027–38.
Leach FS, Nicolaides NC, Papadopoulos N,et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 1993;75:1215–25.
Peltomaki P, Vasen HF. Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Gastroenterology 1997;113:1146–58.
Nicolaides NC, Papadopoulos N, Liu B,et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 1994;371:75–80.
Akiyama Y, Sato H, Yamada T,et al. Germ-line mutation of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred. Cancer Res 1997;57:3920–3.
Miyaki M, Konishi M, Tanaka K,et al. Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet 1997;17:271–2.
Prolla TA, Baker SM, Harris AC,et al. Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nat Genet 1998;18:276–9.
Markowitz S, Wang J, Myeroff L,et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995;268:1336–8.
Foulds L. The natural history of cancer. J Chronic Dis 1958;8:1–37.
Nowell PC. The clonal evolution of tumor cell populations. Science 1976;194:23–8.
Loeb LA. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res 1991;51:3075–9.
Lu SL, Kawabata M, Imamura T,et al. HNPCC associated with germline mutation in the TGF-beta type II receptor gene. Nat Genet 1998;19:17–8.
Dietmaier W, Wallinger S, Bocker T, Kullmann F, Fishel R, Ruschoff J. Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res 1997;57:4749–56.
Aaltonen LA, Peltomaki P, Leach FS,et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993;260:812–6.
Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993:260:816–9.
Nollau P, Wagener C. Methods for detection of point mutations: performance and quality assessment. IFCC Scientific Division, Committee on Molecular Biology Techniques. Clin Chem 1997;43:1114–28.
Gryfe R, Kim H, Hsieh ET,et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000;342:69–77.
Cawkwell L, Gray S, Murgatroyd H,et al. Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair. Gut 1999;45:409–15.
Marcus VA, Madlensky L, Gryfe R,et al. Immunohistochemistry for hMLH1 and hMSH2: A practical test for DNA mismatch-repair deficient tumors. Am J Surg Pathol 1999;23:1248–55.
Powell SM, Petersen GM, Krush AJ,et al. Molecular diagnosis of familial adenomatous polyposis. N Engl J Med 1993;329:1982–7.
Giardiello FM, Brensinger JD, Petersen GM,et al. The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. N Engl J Med 1997;336:823–7.
Wijnen J, van der Klift H, Vasen H,et al. MSH2 genomic deletions are a frequent cause of HNPCC. Nat Genet 1998;20:326–8.
Mauillon JL, Michel P, Limacher JM,et al. Identification of novel germ line hMLH1 mutations including a 22 kb alu-mediated deletion in patients with familial colorectal cancer. Cancer Res 1996;56:5728–33.
Liu B, Parsons R, Papadopoulos N,et al. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med 1996;2:169–74.
Shimodaira H, Filosi N, Shibata H,et al. Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae. Nat Genet 1998;19:384–9.
Yuan ZQ, Wong N, Foulkes W,et al. A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish HNPCC kindred: implications for clinical screening. J Med Genet 1999;36:790–3.
Eng C, Vijg J. Genetic testing: the problems and the promise. Nat Biotechnol 1997;15:422–6.
Wilgenbus KK, Lichter P. DNA chip technologyante portas. J Mol Med 1999;77:761–8.
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Rabelo, R., Foulkes, W., Gordon, P.H. et al. Role of molecular diagnostic testing in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer families. Dis Colon Rectum 44, 437–446 (2001). https://doi.org/10.1007/BF02234746
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DOI: https://doi.org/10.1007/BF02234746