Tags

Type your tag names separated by a space and hit enter

Genomic DNA-based hMSH2 and hMLH1 mutation screening in 32 Eastern United States hereditary nonpolyposis colorectal cancer pedigrees.
Cancer Res. 1997 Sep 01; 57(17):3798-803.CR

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early age of onset colorectal cancer (mean 45 years) as well as endometrial, urinary tract, and upper gastrointestinal adenocarcinomas. The HNPCC phenotype has been shown to segregate with germline mutations in the human homologues of the DNA mismatch repair genes MSH2, MLH1, PMS1, and PMS2. However, the majority of published DNA mismatch repair gene mutation surveys associated with HNPCC kindreds report multiple levels of preselection, including 2p and 3p chromosomal linkage analysis and the evaluation of microsatellite instability of proband colorectal cancers prior to mutation analysis. For this reason, the concise contribution of each of the known DNA mismatch repair genes to the HNPCC phenotype remains unknown. We report the results of a genomic DNA-based analysis of hMSH2 and hMLH1 germline mutations in 32 unrelated Eastern United States HNPCC kindreds. These families were selected for study on the basis of phenotype only. We identified three hMSH2 and six hMLH1 mutations in eight families, for a positive mutation rate of 25%. Two mutations were identified in one of the families. Four of the mutations detected have not been reported in the literature previously. One of the mutation-positive families is African American; the others were of European-American ancestry. These results provide a clarification of the contribution of hMSH2 and hMLH1 to the HNPCC phenotype and suggest that in the majority of Eastern United States HNPCC kindreds selected by phenotype alone, the molecular genetic basis for the disease remains unknown.

Authors+Show Affiliations

Department of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9288790

Citation

Weber, T K., et al. "Genomic DNA-based hMSH2 and hMLH1 Mutation Screening in 32 Eastern United States Hereditary Nonpolyposis Colorectal Cancer Pedigrees." Cancer Research, vol. 57, no. 17, 1997, pp. 3798-803.
Weber TK, Conlon W, Petrelli NJ, et al. Genomic DNA-based hMSH2 and hMLH1 mutation screening in 32 Eastern United States hereditary nonpolyposis colorectal cancer pedigrees. Cancer Res. 1997;57(17):3798-803.
Weber, T. K., Conlon, W., Petrelli, N. J., Rodriguez-Bigas, M., Keitz, B., Pazik, J., Farrell, C., O'Malley, L., Oshalim, M., Abdo, M., Anderson, G., Stoler, D., & Yandell, D. (1997). Genomic DNA-based hMSH2 and hMLH1 mutation screening in 32 Eastern United States hereditary nonpolyposis colorectal cancer pedigrees. Cancer Research, 57(17), 3798-803.
Weber TK, et al. Genomic DNA-based hMSH2 and hMLH1 Mutation Screening in 32 Eastern United States Hereditary Nonpolyposis Colorectal Cancer Pedigrees. Cancer Res. 1997 Sep 1;57(17):3798-803. PubMed PMID: 9288790.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genomic DNA-based hMSH2 and hMLH1 mutation screening in 32 Eastern United States hereditary nonpolyposis colorectal cancer pedigrees. AU - Weber,T K, AU - Conlon,W, AU - Petrelli,N J, AU - Rodriguez-Bigas,M, AU - Keitz,B, AU - Pazik,J, AU - Farrell,C, AU - O'Malley,L, AU - Oshalim,M, AU - Abdo,M, AU - Anderson,G, AU - Stoler,D, AU - Yandell,D, PY - 1997/9/1/pubmed PY - 1997/9/1/medline PY - 1997/9/1/entrez SP - 3798 EP - 803 JF - Cancer research JO - Cancer Res. VL - 57 IS - 17 N2 - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early age of onset colorectal cancer (mean 45 years) as well as endometrial, urinary tract, and upper gastrointestinal adenocarcinomas. The HNPCC phenotype has been shown to segregate with germline mutations in the human homologues of the DNA mismatch repair genes MSH2, MLH1, PMS1, and PMS2. However, the majority of published DNA mismatch repair gene mutation surveys associated with HNPCC kindreds report multiple levels of preselection, including 2p and 3p chromosomal linkage analysis and the evaluation of microsatellite instability of proband colorectal cancers prior to mutation analysis. For this reason, the concise contribution of each of the known DNA mismatch repair genes to the HNPCC phenotype remains unknown. We report the results of a genomic DNA-based analysis of hMSH2 and hMLH1 germline mutations in 32 unrelated Eastern United States HNPCC kindreds. These families were selected for study on the basis of phenotype only. We identified three hMSH2 and six hMLH1 mutations in eight families, for a positive mutation rate of 25%. Two mutations were identified in one of the families. Four of the mutations detected have not been reported in the literature previously. One of the mutation-positive families is African American; the others were of European-American ancestry. These results provide a clarification of the contribution of hMSH2 and hMLH1 to the HNPCC phenotype and suggest that in the majority of Eastern United States HNPCC kindreds selected by phenotype alone, the molecular genetic basis for the disease remains unknown. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/9288790/Genomic_DNA_based_hMSH2_and_hMLH1_mutation_screening_in_32_Eastern_United_States_hereditary_nonpolyposis_colorectal_cancer_pedigrees_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=9288790 DB - PRIME DP - Unbound Medicine ER -