Mutations predisposing to hereditary nonpolyposis colorectal cancer: Database and results of a collaborative study

P. Peltomaki, H. F A Vasen, M. L. Bisgaard, J. M. Buerstedde, W. Friedl, S. Grandjouan, P. Hutter, M. Kohonen-Corish, R. Kolodner, G. Kurzawski, A. Lindblom, Henry T. Lynch, A. Piepoli, M. P. De Leon, P. Radice, S. Thibodeau, W. Weber, S. West, J. Wijnen

Research output: Contribution to journalArticle

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Abstract

Background and Aims: Germline mutations in four DNA mismatch repair genes are known to cause susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC). The rapidly increasing information about these mutations needs to be collected and appropriately stored to facilitate further studies on the biological and clinical significance of the findings. Methods: The International Collaborative Group on HNPCC has established a database of DNA mismatch repair gene mutations and polymorphisms. In this report, 126 predisposing mutations were analyzed. Results: A majority of the mutations affected either the Mut L homologue (MLH) 1 (n = 75) or the Mut S homologue (MSH) 2 (n = 48) and were quite evenly distributed, with some clustering in MSH2 exon 12 and MLH1 exon 16. Most MSH2 mutations consisted of frameshift (60%) or non sense changes (23%), whereas MLH1 was mainly affected by frameshift (40%) or missense alterations (31%). Although most mutations were unique, a few common recurring mutations were identified. Of the families studied (n = 202), 82% met the Amsterdam criteria and 15% did not: the general mutation profile was similar in both groups. Conclusions: The construction of mutation profiles will facilitate the development of diagnostic strategies in HNPCC.

Original languageEnglish
Pages (from-to)1146-1158
Number of pages13
JournalGastroenterology
Volume113
Issue number4
DOIs
StatePublished - 1997
Externally publishedYes

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Hereditary Nonpolyposis Colorectal Neoplasms
Databases
Mutation
DNA Mismatch Repair
Exons
Frameshift Mutation
Germ-Line Mutation
Genes
Cluster Analysis

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Peltomaki, P., Vasen, H. F. A., Bisgaard, M. L., Buerstedde, J. M., Friedl, W., Grandjouan, S., ... Wijnen, J. (1997). Mutations predisposing to hereditary nonpolyposis colorectal cancer: Database and results of a collaborative study. Gastroenterology, 113(4), 1146-1158. https://doi.org/10.1053/gast.1997.v113.pm9322509

Mutations predisposing to hereditary nonpolyposis colorectal cancer : Database and results of a collaborative study. / Peltomaki, P.; Vasen, H. F A; Bisgaard, M. L.; Buerstedde, J. M.; Friedl, W.; Grandjouan, S.; Hutter, P.; Kohonen-Corish, M.; Kolodner, R.; Kurzawski, G.; Lindblom, A.; Lynch, Henry T.; Piepoli, A.; De Leon, M. P.; Radice, P.; Thibodeau, S.; Weber, W.; West, S.; Wijnen, J.

In: Gastroenterology, Vol. 113, No. 4, 1997, p. 1146-1158.

Research output: Contribution to journalArticle

Peltomaki, P, Vasen, HFA, Bisgaard, ML, Buerstedde, JM, Friedl, W, Grandjouan, S, Hutter, P, Kohonen-Corish, M, Kolodner, R, Kurzawski, G, Lindblom, A, Lynch, HT, Piepoli, A, De Leon, MP, Radice, P, Thibodeau, S, Weber, W, West, S & Wijnen, J 1997, 'Mutations predisposing to hereditary nonpolyposis colorectal cancer: Database and results of a collaborative study', Gastroenterology, vol. 113, no. 4, pp. 1146-1158. https://doi.org/10.1053/gast.1997.v113.pm9322509
Peltomaki, P. ; Vasen, H. F A ; Bisgaard, M. L. ; Buerstedde, J. M. ; Friedl, W. ; Grandjouan, S. ; Hutter, P. ; Kohonen-Corish, M. ; Kolodner, R. ; Kurzawski, G. ; Lindblom, A. ; Lynch, Henry T. ; Piepoli, A. ; De Leon, M. P. ; Radice, P. ; Thibodeau, S. ; Weber, W. ; West, S. ; Wijnen, J. / Mutations predisposing to hereditary nonpolyposis colorectal cancer : Database and results of a collaborative study. In: Gastroenterology. 1997 ; Vol. 113, No. 4. pp. 1146-1158.
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abstract = "Background and Aims: Germline mutations in four DNA mismatch repair genes are known to cause susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC). The rapidly increasing information about these mutations needs to be collected and appropriately stored to facilitate further studies on the biological and clinical significance of the findings. Methods: The International Collaborative Group on HNPCC has established a database of DNA mismatch repair gene mutations and polymorphisms. In this report, 126 predisposing mutations were analyzed. Results: A majority of the mutations affected either the Mut L homologue (MLH) 1 (n = 75) or the Mut S homologue (MSH) 2 (n = 48) and were quite evenly distributed, with some clustering in MSH2 exon 12 and MLH1 exon 16. Most MSH2 mutations consisted of frameshift (60{\%}) or non sense changes (23{\%}), whereas MLH1 was mainly affected by frameshift (40{\%}) or missense alterations (31{\%}). Although most mutations were unique, a few common recurring mutations were identified. Of the families studied (n = 202), 82{\%} met the Amsterdam criteria and 15{\%} did not: the general mutation profile was similar in both groups. Conclusions: The construction of mutation profiles will facilitate the development of diagnostic strategies in HNPCC.",
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T1 - Mutations predisposing to hereditary nonpolyposis colorectal cancer

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AU - Peltomaki, P.

AU - Vasen, H. F A

AU - Bisgaard, M. L.

AU - Buerstedde, J. M.

AU - Friedl, W.

AU - Grandjouan, S.

AU - Hutter, P.

AU - Kohonen-Corish, M.

AU - Kolodner, R.

AU - Kurzawski, G.

AU - Lindblom, A.

AU - Lynch, Henry T.

AU - Piepoli, A.

AU - De Leon, M. P.

AU - Radice, P.

AU - Thibodeau, S.

AU - Weber, W.

AU - West, S.

AU - Wijnen, J.

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