FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Volume 338:1481-1487 May 21, 1998 Number 21 Next

	Full Text PDF Editorial by Lynch, H. T. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Genetic disorders that predispose people to colorectal cancer include the polyposis syndromes and hereditary nonpolyposis colorectal cancer. In contrast to the polyposis syndromes, hereditary nonpolyposis colorectal cancer lacks distinctive clinical features. However, a germ-line mutation of DNA mismatch-repair genes is a characteristic molecular feature of the disease. Since clinical screening of carriers of such mutations can help prevent cancer, it is important to devise strategies applicable to molecular screening for this disease.

Methods We prospectively screened tumor specimens obtained from 509 consecutive patients with colorectal adenocarcinomas for DNA replication errors, which are characteristic of hereditary colorectal cancers. These replication errors were detected through microsatellite-marker analyses of tumor DNA. DNA from normal tissue from the patients with replication errors was screened for germ-line mutations of the mismatch-repair genes MLH1 and MSH2.

Results Among the 509 patients, 63 (12 percent) had replication errors. Specimens of normal tissue from 10 of these 63 patients had a germ-line mutation of MLH1 or MSH2. Of these 10 patients (2 percent of the 509 patients), 9 had a first-degree relative with endometrial or colorectal cancer, 7 were under 50 years of age, and 4 had had colorectal or endometrial cancer previously.

Conclusions In this series of patients with colorectal cancer in Finland, at least 2 percent had hereditary nonpolyposis colorectal cancer. We recommend testing for replication errors in all patients with colorectal cancer who meet one or more of the following criteria: a family history of colorectal or endometrial cancer, an age of less than 50 years, and a history of multiple colorectal or endometrial cancers. Patients found to have replication errors should undergo further analysis for germ-line mutations in DNA mismatch-repair genes.

Source Information

From the Departments of Medical Genetics (L.A.A., R.S., P.K., F.C., A.H., P.P., A.C.) and Pathology (R.S.), Haartman Institute, University of Helsinki, Helsinki, Finland; Applied Biosystems Division, Perkin–Elmer Corporation, Foster City, Calif. (R.B.C.); the Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, Columbus (R.B.C., A.C.); the Family Federation of Finland, Helsinki (H.K.); the Department of Surgery, Central Hospital of Jyväskylä, Jyväskylä, Finland (J.-P.M.); the Department of Surgery, Kuopio University Hospital, Kuopio, Finland (M.E.); and the Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland (H.J.). Other authors were Antonio Percesepe, M.D. (Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki), Heikki Ahtola, M.D. (Department of Surgery, Central Hospital of Joensuu, Joensuu), Niilo Härkönen, M.D. (Department of Surgery, Central Hospital of Mikkeli, Mikkeli), Risto Julkunen, M.D. (Department of Internal Medicine, Kuopio University Hospital, Kuopio), Eero Kangas, M.D. (Department of Surgery, Central Hospital of Lappenranta, Lappenranta), Seppo Ojala, M.D. (Department of Surgery, Central Hospital of Kajaani, Kajaani), Jukka Tulikoura, M.D. (Department of Surgery, Central Hospital of Kotka, Kotka), and Erkki Valkamo, M.D. (Department of Surgery, Central Hospital of Savonlinna, Savonlinna) — all in Finland.

Address reprint requests to Dr. Aaltonen at the Department of Medical Genetics, Haartman Institute, P.O. Box 21, FIN-00014 University of Helsinki, Helsinki, Finland.

Full Text of this Article

Related Letters:

Molecular Diagnosis of Hereditary Nonpolyposis Colon Cancer
Guillem J. G., Aaltonen L. A., Mecklin J.-P., de la Chapelle A.
Extract | Full Text  
N Engl J Med 1998; 339:924-925, Sep 24, 1998. Correspondence

This article has been cited by other articles:

• Vilar, E., Mukherjee, B., Kuick, R., Raskin, L., Misek, D. E., Taylor, J. M.G., Giordano, T. J., Hanash, S. M., Fearon, E. R., Rennert, G., Gruber, S. B. (2009). Gene Expression Patterns in Mismatch Repair-Deficient Colorectal Cancers Highlight the Potential Therapeutic Role of Inhibitors of the Phosphatidylinositol 3-Kinase-AKT-Mammalian Target of Rapamycin Pathway. Clin. Cancer Res. 15: 2829-2839 [Abstract] [Full Text]  
• Botteri, E., Iodice, S., Bagnardi, V., Raimondi, S., Lowenfels, A. B., Maisonneuve, P. (2008). Smoking and Colorectal Cancer: A Meta-analysis. JAMA 300: 2765-2778 [Abstract] [Full Text]  
• Poynter, J. N., Siegmund, K. D., Weisenberger, D. J., Long, T. I., Thibodeau, S. N., Lindor, N., Young, J., Jenkins, M. A., Hopper, J. L., Baron, J. A., Buchanan, D., Casey, G., Levine, A. J., Marchand, L. L., Gallinger, S., Bapat, B., Potter, J. D., Newcomb, P. A., Haile, R. W., Laird, P. W., for the Colon Cancer Family Registry Investigators, (2008). Molecular Characterization of MSI-H Colorectal Cancer by MLHI Promoter Methylation, Immunohistochemistry, and Mismatch Repair Germline Mutation Screening. Cancer Epidemiol. Biomarkers Prev. 17: 3208-3215 [Abstract] [Full Text]  
• Ramsoekh, D, Wagner, A, van Leerdam, M E, Dinjens, W N M, Steyerberg, E W, Halley, D J J, Kuipers, E J, Dooijes, D (2008). A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting. Gut 57: 1539-1544 [Abstract] [Full Text]  
• Balmana, J, Balaguer, F, Castellvi-Bel, S, Steyerberg, E W, Andreu, M, Llor, X, Jover, R, Castells, A, Syngal, S, for the Gastrointestinal Oncology Group of the Spa, (2008). Comparison of predictive models, clinical criteria and molecular tumour screening for the identification of patients with Lynch syndrome in a population-based cohort of colorectal cancer patients. J. Med. Genet. 45: 557-563 [Abstract] [Full Text]  
• Thomas, A. MD, Lenox, R. MD (2008). Pulmonary lymphangitic carcinomatosis as a primary manifestation of colon cancer in a young adult. CMAJ 179: 338-340 [Abstract] [Full Text]  
• Zhang, L. (2008). Immunohistochemistry versus Microsatellite Instability Testing for Screening Colorectal Cancer Patients at Risk for Hereditary Nonpolyposis Colorectal Cancer Syndrome: Part II. The Utility of Microsatellite Instability Testing. J. Mol. Diagn. 10: 301-307 [Abstract] [Full Text]  
• French, A. J., Sargent, D. J., Burgart, L. J., Foster, N. R., Kabat, B. F., Goldberg, R., Shepherd, L., Windschitl, H. E., Thibodeau, S. N. (2008). Prognostic Significance of Defective Mismatch Repair and BRAF V600E in Patients with Colon Cancer. Clin. Cancer Res. 14: 3408-3415 [Abstract] [Full Text]  
• Alhopuro, P., Phichith, D., Tuupanen, S., Sammalkorpi, H., Nybondas, M., Saharinen, J., Robinson, J. P., Yang, Z., Chen, L.-Q., Orntoft, T., Mecklin, J.-P., Jarvinen, H., Eng, C., Moeslein, G., Shibata, D., Houlston, R. S., Lucassen, A., Tomlinson, I. P. M., Launonen, V., Ristimaki, A., Arango, D., Karhu, A., Sweeney, H. L., Aaltonen, L. A. (2008). Unregulated smooth-muscle myosin in human intestinal neoplasia. Proc. Natl. Acad. Sci. USA 105: 5513-5518 [Abstract] [Full Text]  
• Tuupanen, S., Niittymaki, I., Nousiainen, K., Vanharanta, S., Mecklin, J.-P., Nuorva, K., Jarvinen, H., Hautaniemi, S., Karhu, A., Aaltonen, L. A. (2008). Allelic Imbalance at rs6983267 Suggests Selection of the Risk Allele in Somatic Colorectal Tumor Evolution. Cancer Res. 68: 14-17 [Abstract] [Full Text]  
• Balmana, J., Steyerberg, E. W., Syngal, S. (2008). Risk Quantification for Carrying Mutations in Lynch Syndrome Genes. Am Soc Clin Oncol Ed Book 2008: 59-64 [Abstract] [Full Text]  
• Yang, Q., Zhang, R., Horikawa, I., Fujita, K., Afshar, Y., Kokko, A., Laiho, P., Aaltonen, L. A., Harris, C. C. (2007). Functional Diversity of Human Protection of Telomeres 1 Isoforms in Telomere Protection and Cellular Senescence. Cancer Res. 67: 11677-11686 [Abstract] [Full Text]  
• Sanchez-de-Abajo, A., de la Hoya, M., van Puijenbroek, M., Tosar, A., Lopez-Asenjo, J.A., Diaz-Rubio, E., Morreau, H., Caldes, T. (2007). Molecular Analysis of Colorectal Cancer Tumors from Patients with Mismatch Repair Proficient Hereditary Nonpolyposis Colorectal Cancer Suggests Novel Carcinogenic Pathways. Clin. Cancer Res. 13: 5729-5735 [Abstract] [Full Text]  
• Pande, M., Chen, J., Amos, C. I., Lynch, P. M., Broaddus, R., Frazier, M. L. (2007). Influence of Methylenetetrahydrofolate Reductase Gene Polymorphisms C677T and A1298C on Age-Associated Risk for Colorectal Cancer in a Caucasian Lynch Syndrome Population. Cancer Epidemiol. Biomarkers Prev. 16: 1753-1759 [Abstract] [Full Text]  
• Watson, N., Grieu, F., Morris, M., Harvey, J., Stewart, C., Schofield, L., Goldblatt, J., Iacopetta, B. (2007). Heterogeneous Staining for Mismatch Repair Proteins during Population-Based Prescreening for Hereditary Nonpolyposis Colorectal Cancer. J. Mol. Diagn. 9: 472-478 [Abstract] [Full Text]  
• Laakso, M., Tuupanen, S., Karhu, A., Lehtonen, R., Aaltonen, L. A., Hautaniemi, S. (2007). Computational identification of candidate loci for recessively inherited mutation using high-throughput SNP arrays. Bioinformatics 23: 1952-1961 [Abstract] [Full Text]  
• Malesci, A., Laghi, L., Bianchi, P., Delconte, G., Randolph, A., Torri, V., Carnaghi, C., Doci, R., Rosati, R., Montorsi, M., Roncalli, M., Gennari, L., Santoro, A. (2007). Reduced Likelihood of Metastases in Patients with Microsatellite-Unstable Colorectal Cancer. Clin. Cancer Res. 13: 3831-3839 [Abstract] [Full Text]  
• Sammalkorpi, H., Alhopuro, P., Lehtonen, R., Tuimala, J., Mecklin, J.-P., Jarvinen, H. J., Jiricny, J., Karhu, A., Aaltonen, L. A. (2007). Background Mutation Frequency in Microsatellite-Unstable Colorectal Cancer. Cancer Res. 67: 5691-5698 [Abstract] [Full Text]  
• Vasen, H F A, Moslein, G, Alonso, A, Bernstein, I, Bertario, L, Blanco, I, Burn, J, Capella, G, Engel, C, Frayling, I, Friedl, W, Hes, F J, Hodgson, S, Mecklin, J-P, Moller, P, Nagengast, F, Parc, Y, Renkonen-Sinisalo, L, Sampson, J R, Stormorken, A, Wijnen, J (2007). Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J. Med. Genet. 44: 353-362 [Abstract] [Full Text]  
• Valle, L., Perea, J., Carbonell, P., Fernandez, V., Dotor, A. M., Benitez, J., Urioste, M. (2007). Clinicopathologic and Pedigree Differences in Amsterdam I-Positive Hereditary Nonpolyposis Colorectal Cancer Families According to Tumor Microsatellite Instability Status. JCO 25: 781-786 [Abstract] [Full Text]  
• Lynch, H. T., Lynch, J. F., Lynch, P. M. (2007). Toward a Consensus in Molecular Diagnosis of Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome). JNCI J Natl Cancer Inst 99: 261-263 [Full Text]  
• Wanat, J. J., Singh, N., Alani, E. (2007). The effect of genetic background on the function of Saccharomyces cerevisiae mlh1 alleles that correspond to HNPCC missense mutations. Hum Mol Genet 16: 445-452 [Abstract] [Full Text]  
• Aaltonen, L., Johns, L., Jarvinen, H., Mecklin, J.-P., Houlston, R. (2007). Explaining the Familial Colorectal Cancer Risk Associated with Mismatch Repair (MMR)-Deficient and MMR-Stable Tumors. Clin. Cancer Res. 13: 356-361 [Abstract] [Full Text]  
• Niessen, R C, Berends, M J W, Wu, Y, Sijmons, R H, Hollema, H, Ligtenberg, M J L, de Walle, H E K, de Vries, E G E, Karrenbeld, A, Buys, C H C M, van der Zee, A G J, Hofstra, R M W, Kleibeuker, J H (2006). Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer. Gut 55: 1781-1788 [Abstract] [Full Text]  
• Benlloch, S., Paya, A., Alenda, C., Bessa, X., Andreu, M., Jover, R., Castells, A., Llor, X., Aranda, F. I., Massuti, B. (2006). Detection of BRAF V600E Mutation in Colorectal Cancer: Comparison of Automatic Sequencing and Real-Time Chemistry Methodology. J. Mol. Diagn. 8: 540-543 [Abstract] [Full Text]  
• Balmana, J., Stockwell, D. H., Steyerberg, E. W., Stoffel, E. M., Deffenbaugh, A. M., Reid, J. E., Ward, B., Scholl, T., Hendrickson, B., Tazelaar, J., Burbidge, L. A., Syngal, S. (2006). Prediction of MLH1 and MSH2 mutations in Lynch syndrome.. JAMA 296: 1469-1478 [Abstract] [Full Text]  
• Lindor, N. M., Petersen, G. M., Hadley, D. W., Kinney, A. Y., Miesfeldt, S., Lu, K. H., Lynch, P., Burke, W., Press, N. (2006). Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review.. JAMA 296: 1507-1517 [Abstract] [Full Text]  
• Goecke, T., Schulmann, K., Engel, C., Holinski-Feder, E., Pagenstecher, C., Schackert, H. K., Kloor, M., Kunstmann, E., Vogelsang, H., Keller, G., Dietmaier, W., Mangold, E., Friedrichs, N., Propping, P., Kruger, S., Gebert, J., Schmiegel, W., Rueschoff, J., Loeffler, M., Moeslein, G. (2006). Genotype-Phenotype Comparison of German MLH1 and MSH2 Mutation Carriers Clinically Affected With Lynch Syndrome: A Report by the German HNPCC Consortium. JCO 24: 4285-4292 [Abstract] [Full Text]  
• Kilpivaara, O, Alhopuro, P, Vahteristo, P, Aaltonen, L A, Nevanlinna, H (2006). CHEK2 I157T associates with familial and sporadic colorectal cancer.. J. Med. Genet. 43: e34-e34 [Abstract] [Full Text]  
• Barnetson, R. A., Tenesa, A., Farrington, S. M., Nicholl, I. D., Cetnarskyj, R., Porteous, M. E., Campbell, H., Dunlop, M. G. (2006). Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer.. NEJM 354: 2751-2763 [Abstract] [Full Text]  
• Buhard, O., Cattaneo, F., Wong, Y. F., Yim, S. F., Friedman, E., Flejou, J.-F., Duval, A., Hamelin, R. (2006). Multipopulation Analysis of Polymorphisms in Five Mononucleotide Repeats Used to Determine the Microsatellite Instability Status of Human Tumors. JCO 24: 241-251 [Abstract] [Full Text]  
• Alazzouzi, H., Davalos, V., Kokko, A., Domingo, E., Woerner, S. M., Wilson, A. J., Konrad, L., Laiho, P., Espin, E., Armengol, M., Imai, K., Yamamoto, H., Mariadason, J. M., Gebert, J. F., Aaltonen, L. A., Schwartz, S. Jr., Arango, D. (2005). Mechanisms of Inactivation of the Receptor Tyrosine Kinase EPHB2 in Colorectal Tumors. Cancer Res. 65: 10170-10173 [Abstract] [Full Text]  
• Judkins, T., Hendrickson, B. C., Deffenbaugh, A. M., Eliason, K., Leclair, B., Norton, M. J., Ward, B. E., Pruss, D., Scholl, T. (2005). Application of Embryonic Lethal or Other Obvious Phenotypes to Characterize the Clinical Significance of Genetic Variants Found in Trans with Known Deleterious Mutations. Cancer Res. 65: 10096-10103 [Abstract] [Full Text]  
• Sotamaa, K., Liyanarachchi, S., Mecklin, J.-P., Jarvinen, H., Aaltonen, L. A., Peltomaki, P., de la Chapelle, A. (2005). p53 Codon 72 and MDM2 SNP309 Polymorphisms and Age of Colorectal Cancer Onset in Lynch Syndrome. Clin. Cancer Res. 11: 6840-6844 [Abstract] [Full Text]  
• Woods, M. O., Hyde, A. J., Curtis, F. K., Stuckless, S., Green, J. S., Pollett, A. F., Robb, J. D., Green, R. C., Croitoru, M. E., Careen, A., Chaulk, J. A.W., Jegathesan, J., McLaughlin, J. R., Gallinger, S. S., Younghusband, H. B., Bapat, B. V., Parfrey, P. S. (2005). High Frequency of Hereditary Colorectal Cancer in Newfoundland Likely Involves Novel Susceptibility Genes. Clin. Cancer Res. 11: 6853-6861 [Abstract] [Full Text]  
• Alhopuro, P, Ylisaukko-oja, S K, Koskinen, W J, Bono, P, Arola, J, Jarvinen, H J, Mecklin, J-P, Atula, T, Kontio, R, Makitie, A A, Suominen, S, Leivo, I, Vahteristo, P, Aaltonen, L-M, Aaltonen, L A (2005). The MDM2 promoter polymorphism SNP309T->G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck. J. Med. Genet. 42: 694-698 [Abstract] [Full Text]  
• Alhopuro, P., Alazzouzi, H., Sammalkorpi, H., Davalos, V., Salovaara, R., Hemminki, A., Jarvinen, H., Mecklin, J.-P., Schwartz, S. Jr., Aaltonen, L. A., Arango, D. (2005). SMAD4 Levels and Response to 5-Fluorouracil in Colorectal Cancer. Clin. Cancer Res. 11: 6311-6316 [Abstract] [Full Text]  
• Ollikainen, M., Abdel-Rahman, W. M., Moisio, A.-L., Lindroos, A., Kariola, R., Jarvela, I., Poyhonen, M., Butzow, R., Peltomaki, P. (2005). Molecular Analysis of Familial Endometrial Carcinoma: A Manifestation of Hereditary Nonpolyposis Colorectal Cancer or a Separate Syndrome?. JCO 23: 4609-4616 [Abstract] [Full Text]  
• Wark, P. A., Weijenberg, M. P., van 't Veer, P., van Wijhe, G., Luchtenborg, M., van Muijen, G. N.P., de Goeij, A. F.P.M., Goldbohm, R. A., van den Brandt, P. A. (2005). Fruits, Vegetables, and hMLH1 Protein-Deficient and -Proficient Colon Cancer: The Netherlands Cohort Study. Cancer Epidemiol. Biomarkers Prev. 14: 1619-1625 [Abstract] [Full Text]  
• Chen, S., Watson, P., Parmigiani, G. (2005). Accuracy of MSI testing in predicting germline mutations of MSH2 and MLH1: a case study in Bayesian meta-analysis of diagnostic tests without a gold standard. Biostatistics 6: 450-464 [Abstract] [Full Text]  
• Hienonen, T., Sammalkorpi, H., Enholm, S., Alhopuro, P., Barber, T. D., Lehtonen, R., Nupponen, N. N., Lehtonen, H., Salovaara, R., Mecklin, J.-P., Jarvinen, H., Koistinen, R., Arango, D., Launonen, V., Vogelstein, B., Karhu, A., Aaltonen, L. A. (2005). Mutations in Two Short Noncoding Mononucleotide Repeats in Most Microsatellite-Unstable Colorectal Cancers. Cancer Res. 65: 4607-4613 [Abstract] [Full Text]  
• Hampel, H., Frankel, W. L., Martin, E., Arnold, M., Khanduja, K., Kuebler, P., Nakagawa, H., Sotamaa, K., Prior, T. W., Westman, J., Panescu, J., Fix, D., Lockman, J., Comeras, I., de la Chapelle, A. (2005). Screening for the Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer). NEJM 352: 1851-1860 [Abstract] [Full Text]  
• Lynch, H. T., Lynch, P. M. (2005). Molecular Screening for the Lynch Syndrome -- Better Than Family History?. NEJM 352: 1920-1922 [Full Text]  
• Pinol, V., Castells, A., Andreu, M., Castellvi-Bel, S., Alenda, C., Llor, X., Xicola, R. M., Rodriguez-Moranta, F., Paya, A., Jover, R., Bessa, X., for the Gastrointestinal Oncology Group of the Spa, (2005). Accuracy of Revised Bethesda Guidelines, Microsatellite Instability, and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer. JAMA 293: 1986-1994 [Abstract] [Full Text]  
• Vahteristo, P, Ojala, S, Tamminen, A, Tommiska, J, Sammalkorpi, H, Kiuru-Kuhlefelt, S, Eerola, H, Aaltonen, L A, Aittomaki, K, Nevanlinna, H (2005). No MSH6 germline mutations in breast cancer families with colorectal and/or endometrial cancer. J. Med. Genet. 42: e22-e22 [Abstract] [Full Text]  
• Alazzouzi, H., Alhopuro, P., Salovaara, R., Sammalkorpi, H., Jarvinen, H., Mecklin, J.-P., Hemminki, A., Schwartz, S. Jr., Aaltonen, L. A., Arango, D. (2005). SMAD4 as a Prognostic Marker in Colorectal Cancer. Clin. Cancer Res. 11: 2606-2611 [Abstract] [Full Text]  
• Chen, Y.-C., Hunter, D. J. (2005). Molecular Epidemiology of Cancer. CA Cancer J Clin 55: 45-54 [Abstract] [Full Text]  
• Croitoru, M. E., Cleary, S. P., Di Nicola, N., Manno, M., Selander, T., Aronson, M., Redston, M., Cotterchio, M., Knight, J., Gryfe, R., Gallinger, S. (2004). Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk. JNCI J Natl Cancer Inst 96: 1631-1634 [Abstract] [Full Text]  
• Alhopuro, P., Ahvenainen, T., Mecklin, J.-P., Juhola, M., Jarvinen, H. J., Karhu, A., Aaltonen, L. A. (2004). NOD2 3020insC Alone Is Not Sufficient for Colorectal Cancer Predisposition. Cancer Res. 64: 7245-7247 [Abstract] [Full Text]  
• Oliveira, C., Westra, J. L., Arango, D., Ollikainen, M., Domingo, E., Ferreira, A., Velho, S., Niessen, R., Lagerstedt, K., Alhopuro, P., Laiho, P., Veiga, I., Teixeira, M. R., Ligtenberg, M., Kleibeuker, J. H., Sijmons, R. H., Plukker, J. T., Imai, K., Lage, P., Hamelin, R., Albuquerque, C., Schwartz, S. Jr, Lindblom, A., Peltomaki, P., Yamamoto, H., Aaltonen, L. A., Seruca, R., Hofstra, R. M.W. (2004). Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status. Hum Mol Genet 13: 2303-2311 [Abstract] [Full Text]  
• Halbert, C. H., Lynch, H., Lynch, J., Main, D., Kucharski, S., Rustgi, A. K., Lerman, C. (2004). Colon Cancer Screening Practices Following Genetic Testing for Hereditary Nonpolyposis Colon Cancer (HNPCC) Mutations. Arch Intern Med 164: 1881-1887 [Abstract] [Full Text]  
• Laghi, L., Bianchi, P., Roncalli, M., Malesci, A. (2004). Re: Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability. JNCI J Natl Cancer Inst 96: 1402-1403 [Full Text]  
• Domingo, E, Laiho, P, Ollikainen, M, Pinto, M, Wang, L, French, A J, Westra, J, Frebourg, T, Espin, E, Armengol, M, Hamelin, R, Yamamoto, H, Hofstra, R M W, Seruca, R, Lindblom, A, Peltomaki, P, Thibodeau, S N, Aaltonen, L A, Schwartz, S Jr (2004). BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J. Med. Genet. 41: 664-668 [Abstract] [Full Text]  
• Umar, A., Boland, C. R., Terdiman, J. P., Syngal, S., Chapelle, A. d. l., Ruschoff, J., Fishel, R., Lindor, N. M., Burgart, L. J., Hamelin, R., Hamilton, S. R., Hiatt, R. A., Jass, J., Lindblom, A., Lynch, H. T., Peltomaki, P., Ramsey, S. D., Rodriguez-Bigas, M. A., Vasen, H. F. A., Hawk, E. T., Barrett, J. C., Freedman, A. N., Srivastava, S. (2004). Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability. JNCI J Natl Cancer Inst 96: 261-268 [Abstract] [Full Text]  
• Lynch, H. T., Coronel, S. M., Okimoto, R., Hampel, H., Sweet, K., Lynch, J. F., Barrows, A., Wijnen, J., van der Klift, H., Franken, P., Wagner, A., Fodde, R., de la Chapelle, A. (2004). A Founder Mutation of the MSH2 Gene and Hereditary Nonpolyposis Colorectal Cancer in the United States. JAMA 291: 718-724 [Abstract] [Full Text]  
• Hampel, H, Sweet, K, Westman, J A, Offit, K, Eng, C (2004). Referral for cancer genetics consultation: a review and compilation of risk assessment criteria. J. Med. Genet. 41: 81-91 [Abstract] [Full Text]  
• de Jong, A. E., van Puijenbroek, M., Hendriks, Y., Tops, C., Wijnen, J., Ausems, M. G. E. M., Meijers-Heijboer, H., Wagner, A., van Os, T. A. M., Brocker-Vriends, A. H. J. T., Vasen, H. F. A., Morreau, H. (2004). Microsatellite Instability, Immunohistochemistry, and Additional PMS2 Staining in Suspected Hereditary Nonpolyposis Colorectal Cancer. Clin. Cancer Res. 10: 972-980 [Abstract] [Full Text]  
• Ponz de Leon, M, Benatti, P, Borghi, F, Pedroni, M, Scarselli, A, Di Gregorio, C, Losi, L, Viel, A, Genuardi, M, Abbati, G, Rossi, G, Menigatti, M, Lamberti, I, Ponti, G, Roncucci, L (2004). Aetiology of colorectal cancer and relevance of monogenic inheritance. Gut 53: 115-122 [Abstract] [Full Text]  
• Kilpivaara, O, Laiho, P, Aaltonen, L A, Nevanlinna, H (2003). CHEK2 1100delC and colorectal cancer. J. Med. Genet. 40: e110-110 [Full Text]  
• Wang, L., Cunningham, J. M., Winters, J. L., Guenther, J. C., French, A. J., Boardman, L. A., Burgart, L. J., McDonnell, S. K., Schaid, D. J., Thibodeau, S. N. (2003). BRAF Mutations in Colon Cancer Are Not Likely Attributable to Defective DNA Mismatch Repair. Cancer Res. 63: 5209-5212 [Abstract] [Full Text]  
• Enholm, S., Hienonen, T., Suomalainen, A., Lipton, L., Tomlinson, I., Karja, V., Eskelinen, M., Mecklin, J.-P., Karhu, A., Jarvinen, H. J., Aaltonen, L. A. (2003). Proportion and Phenotype of MYH-Associated Colorectal Neoplasia in a Population-Based Series of Finnish Colorectal Cancer Patients. Am. J. Pathol. 163: 827-832 [Abstract] [Full Text]  
• Nash, G.M., Gimbel, M., Shia, J., Culliford, A.T., Nathanson, D.R., Ndubuisi, M., Yamaguchi, Y., Zeng, Z.S., Barany, F., Paty, P.B. (2003). Automated, Multiplex Assay for High-Frequency Microsatellite Instability in Colorectal Cancer. JCO 21: 3105-3112 [Abstract] [Full Text]  
• Ribic, C. M., Sargent, D. J., Moore, M. J., Thibodeau, S. N., French, A. J., Goldberg, R. M., Hamilton, S. R., Laurent-Puig, P., Gryfe, R., Shepherd, L. E., Tu, D., Redston, M., Gallinger, S. (2003). Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer. NEJM 349: 247-257 [Abstract] [Full Text]  
• Pedersen, A, Johansen, C, Gronbaek, M (2003). Relations between amount and type of alcohol and colon and rectal cancer in a Danish population based cohort study. Gut 52: 861-867 [Abstract] [Full Text]  
• Laiho, P, Hienonen, T, Mecklin, J-P, Jarvinen, H, Karhu, A, Launonen, V, Aaltonen, L A (2003). Mutation and LOH analysis of ACO2 in colorectal cancer: no evidence of biallelic genetic inactivation. J. Med. Genet. 40: e73-73 [Full Text]  
• Chung, D. C., Rustgi, A. K. (2003). The Hereditary Nonpolyposis Colorectal Cancer Syndrome: Genetics and Clinical Implications. ANN INTERN MED 138: 560-570 [Abstract] [Full Text]  
• Peltomaki, P. (2003). Role of DNA Mismatch Repair Defects in the Pathogenesis of Human Cancer. JCO 21: 1174-1179 [Abstract] [Full Text]  
• Lynch, H. T., de la Chapelle, A. (2003). Hereditary Colorectal Cancer. NEJM 348: 919-932 [Full Text]  
• Ashktorab, H., Smoot, D. T., Carethers, J. M., Rahmanian, M., Kittles, R., Vosganian, G., Doura, M., Nidhiry, E., Naab, T., Momen, B., Shakhani, S., Giardiello, F. M. (2003). High Incidence of Microsatellite Instability in Colorectal Cancer from African Americans. Clin. Cancer Res. 9: 1112-1117 [Abstract] [Full Text]  
• Ansell, S. M., Ackerman, M. J., Black, J. L., Roberts, L. R., Tefferi, A. (2003). Primer on Medical Genomics Part VI: Genomics and Molecular Genetics in Clinical Practice. Mayo Clin Proc. 78: 307-317 [Abstract]  
• Hendriks, Y., Franken, P., Dierssen, J. W., de Leeuw, W., Wijnen, J., Dreef, E., Tops, C., Breuning, M., Brocker-Vriends, A., Vasen, H., Fodde, R., Morreau, H. (2003). Conventional and Tissue Microarray Immunohistochemical Expression Analysis of Mismatch Repair in Hereditary Colorectal Tumors. Am. J. Pathol. 162: 469-477 [Abstract] [Full Text]  
• Salovaara, R, Roth, S, Loukola, A, Launonen, V, Sistonen, P, Avizienyte, E, Kristo, P, Jarvinen, H, Souchelnytskyi, S, Sarlomo-Rikala, M, Aaltonen, L A (2002). Frequent loss of SMAD4/DPC4 protein in colorectal cancers. Mol. Pathol. 55: 385-388 [Abstract] [Full Text]  
• de Jong, M. M., Nolte, I. M., te Meerman, G. J., van der Graaf, W. T. A., de Vries, E. G. E., Sijmons, R. H., Hofstra, R. M. W., Kleibeuker, J. H. (2002). Low-penetrance Genes and Their Involvement in Colorectal Cancer Susceptibility. Cancer Epidemiol. Biomarkers Prev. 11: 1332-1352 [Abstract] [Full Text]  
• Vilkki, S, Launonen, V, Karhu, A, Sistonen, P, Vastrik, I, Aaltonen, L A (2002). Screening for microsatellite instability target genes in colorectal cancers. J. Med. Genet. 39: 785-789 [Abstract] [Full Text]  
• Dunlop, M G (2002). Guidance on large bowel surveillance for people with two first degree relatives with colorectal cancer or one first degree relative diagnosed with colorectal cancer under 45 years. Gut 51: v17-20 [Full Text]  
• Dunlop, M G (2002). Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome. Gut 51: v21-27 [Full Text]  
• Nakagawa, H., Yan, H., Lockman, J., Hampel, H., Kinzler, K. W., Vogelstein, B., de la Chapelle, A. (2002). Allele Separation Facilitates Interpretation of Potential Splicing Alterations and Genomic Rearrangements. Cancer Res. 62: 4579-4582 [Abstract] [Full Text]  
• Zhou, X.-P., Loukola, A., Salovaara, R., Nystrom-Lahti, M., Peltomaki, P., de la Chapelle, A., Aaltonen, L. A., Eng, C. (2002). PTEN Mutational Spectra, Expression Levels, and Subcellular Localization in Microsatellite Stable and Unstable Colorectal Cancers. Am. J. Pathol. 161: 439-447 [Abstract] [Full Text]  
• Leslie, A, Steele, R J C (2002). Management of colorectal cancer. Postgrad. Med. J. 78: 473-478 [Abstract] [Full Text]  
• Rossi, B. M., Lopes, A., Oliveira Ferreira, F., Nakagawa, W. T., Napoli Ferreira, C. C., Casali da Rocha, J. C., Simpson, C. C., Simpson, A. J. G. (2002). hMLH1 and hMSH2 Gene Mutation in Brazilian Families With Suspected Hereditary Nonpolyposis Colorectal Cancer. Ann. Surg. Oncol. 9: 555-561 [Abstract] [Full Text]  
• Salovaara, R, Roth, S, Loukola, A, Launonen, V, Sistonen, P, Avizienyte, E, Kristo, P, Jarvinen, H, Souchelnytskyi, S, Sarlomo-Rikala, M, Aaltonen, L A (2002). Frequent loss of SMAD4/DPC4 protein in colorectal cancers. Gut 51: 56-59 [Abstract] [Full Text]  
• Lynch, P. M. (2002). Screening Colonoscopy for Family History of Colorectal Cancer: A Growing Consensus. Ann. Surg. Oncol. 9: 425-427 [Full Text]  
• Wahlberg, S. S., Schmeits, J., Thomas, G., Loda, M., Garber, J., Syngal, S., Kolodner, R. D., Fox, E. (2002). Evaluation of Microsatellite Instability and Immunohistochemistry for the Prediction of Germ-Line MSH2 and MLH1 Mutations in Hereditary Nonpolyposis Colon Cancer Families. Cancer Res. 62: 3485-3492 [Abstract] [Full Text]  
• Palicio, M, Balmana, J, Gonzalez, S, Blanco, I, Marcuello, E, Peinado, M A, Julia, G, Germa, J R, Lopez Lopez, J J, Brunet, J, Capella, G (2002). Mismatch repair gene analysis in Catalonian families with colorectal cancer. J. Med. Genet. 39: e29-29 [Full Text]  
• Easson, A. M., Cotterchio, M., Crosby, J. A., Sutherland, H., Dale, D., Aronson, M., Holowaty, E., Gallinger, S. (2002). A Population-Based Study of the Extent of Surgical Resection of Potentially Curable Colon Cancer. Ann. Surg. Oncol. 9: 380-387 [Abstract] [Full Text]  
• Carayol, J, Khlat, M, Maccario, J, Bonaiti-Pellie, C (2002). Hereditary non-polyposis colorectal cancer: current risks of colorectal cancer largely overestimated. J. Med. Genet. 39: 335-339 [Full Text]  
• Zhou, X.-P., Kuismanen, S., Nystrom-Lahti, M., Peltomaki, P., Eng, C. (2002). Distinct PTEN mutational spectra in hereditary non-polyposis colon cancer syndrome-related endometrial carcinomas compared to sporadic microsatellite unstable tumors. Hum Mol Genet 11: 445-450 [Abstract] [Full Text]  
• Laiho, P., Launonen, V., Lahermo, P., Esteller, M., Guo, M., Herman, J. G., Mecklin, J.-P., Jarvinen, H., Sistonen, P., Kim, K.-M., Shibata, D., Houlston, R. S., Aaltonen, L. A. (2002). Low-Level Microsatellite Instability in Most Colorectal Carcinomas. Cancer Res. 62: 1166-1170 [Abstract] [Full Text]  
• Katballe, N, Christensen, M, Wikman, F P, Orntoft, T F, Laurberg, S (2002). Frequency of hereditary non-polyposis colorectal cancer in Danish colorectal cancer patients. Gut 50: 43-51 [Abstract] [Full Text]  
• Pastinen, T., Perola, M., Ignatius, J., Sabatti, C., Tainola, P., Levander, M., Syvanen, A.-C., Peltonen, L. (2001). Dissecting a population genome for targeted screening of disease mutations. Hum Mol Genet 10: 2961-2972 [Abstract] [Full Text]  
• Esteller, M., Fraga, M. F., Guo, M., Garcia-Foncillas, J., Hedenfalk, I., Godwin, A. K., Trojan, J., Vaurs-Barriere, C., Bignon, Y.-J., Ramus, S., Benitez, J., Caldes, T., Akiyama, Y., Yuasa, Y., Launonen, V., Canal, M. J., Rodriguez, R., Capella, G., Peinado, M. A., Borg, A., Aaltonen, L. A., Ponder, B. A., Baylin, S. B., Herman, J. G. (2001). DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet 10: 3001-3007 [Abstract] [Full Text]  
• Raedle, J., Trojan, J., Brieger, A., Weber, N., Schafer, D., Plotz, G., Staib-Sebler, E., Kriener, S., Lorenz, M., Zeuzem, S. (2001). Bethesda Guidelines: Relation to Microsatellite Instability and MLH1 Promoter Methylation in Patients with Colorectal Cancer. ANN INTERN MED 135: 566-576 [Abstract] [Full Text]  
• Percesepe, A., Borghi, F., Menigatti, M., Losi, L., Foroni, M., Di Gregorio, C., Rossi, G., Pedroni, M., Sala, E., Vaccina, F., Roncucci, L., Benatti, P., Viel, A., Genuardi, M., Marra, G., Kristo, P., Peltomaki, P., Ponz de Leon, M. (2001). Molecular Screening for Hereditary Nonpolyposis Colorectal Cancer: A Prospective, Population-Based Study. JCO 19: 3944-3950 [Abstract] [Full Text]  
• Nakagawa, H., Nuovo, G. J., Zervos, E. E., Martin, E. W. Jr., Salovaara, R., Aaltonen, L. A., de la Chapelle, A. (2001). Age-related Hypermethylation of the 5' Region of MLH1 in Normal Colonic Mucosa Is Associated with Microsatellite-unstable Colorectal Cancer Development. Cancer Res. 61: 6991-6995 [Abstract] [Full Text]  
• Hemminki, K., Li, X., Dong, C. (2001). Second Primary Cancers after Sporadic and Familial Colorectal Cancer. Cancer Epidemiol. Biomarkers Prev. 10: 793-798 [Abstract] [Full Text]  
• Xiong, Z., Wu, A. H., Bender, C. M., Tsao, J.-L., Blake, C., Shibata, D., Jones, P. A., Yu, M. C., Ross, R. K., Laird, P. W. (2001). Mismatch Repair Deficiency and CpG Island Hypermethylation in Sporadic Colon Adenocarcinomas. Cancer Epidemiol. Biomarkers Prev. 10: 799-803 [Abstract] [Full Text]  
• Ichikawa, A., Sugano, K., Fujita, S. (2001). DNA Variants of BAT-25 in Japanese, a Locus Frequently Used for Analysis of Microsatellite Instability. Jpn J Clin Oncol 31: 346-348 [Abstract] [Full Text]  
• Chadwick, R. B, Pyatt, R. E, Niemann, T. H, Richards, S. K, Johnson, C. K, Stevens, M. W, Meek, J. E, Hampel, H., Prior, T. W, de la Chapelle, A. (2001). Hereditary and somatic DNA mismatch repair gene mutations in sporadic endometrial carcinoma. J. Med. Genet. 38: 461-466 [Full Text]  
• Loukola, A., Eklin, K., Laiho, P., Salovaara, R., Kristo, P., Jarvinen, H., Mecklin, J.-P., Launonen, V., Aaltonen, L. A. (2001). Microsatellite Marker Analysis in Screening for Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Cancer Res. 61: 4545-4549 [Abstract] [Full Text]  
• Slatkin, M., Bertorelle, G. (2001). The Use of Intraallelic Variability for Testing Neutrality and Estimating Population Growth Rate. Genetics 158: 865-874 [Abstract] [Full Text]