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 language | English (US) |
|---|---|
| Pages (from-to) | 1146-1158 |
| Number of pages | 13 |
| Journal | Gastroenterology |
| Volume | 113 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1997 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Gastroenterology
Cite this
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, H. T.; Piepoli, A.; De Leon, M. P.; Radice, P.; Thibodeau, Stephen N; Weber, W.; West, S.; Wijnen, J.
In: Gastroenterology, Vol. 113, No. 4, 1997, p. 1146-1158.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutations predisposing to hereditary nonpolyposis colorectal cancer
T2 - Database and results of a collaborative study
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, H. T.
AU - Piepoli, A.
AU - De Leon, M. P.
AU - Radice, P.
AU - Thibodeau, Stephen N
AU - Weber, W.
AU - West, S.
AU - Wijnen, J.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=0030882381&partnerID=8YFLogxK
U2 - 10.1053/gast.1997.v113.pm9322509
DO - 10.1053/gast.1997.v113.pm9322509
M3 - Article
C2 - 9322509
AN - SCOPUS:0030882381
VL - 113
SP - 1146
EP - 1158
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 4
ER -