Former Students: Yell Leadersphotograph date: Unknow

BERTARIO, L

BISGAARD, ML

CATS, A

FODDE, R

GRIFFIOEN, G

KHAN, PM

KLEIBEUKER, J

LINDHOUT, D

MEIJERSHEIJBOER, A

MENKO, FH

MOHR, J

NAGENGAST, F

VANDENBROEK, M

VANDERKLIFT, H

VANLEEUWEN, C

VANLEEUWENCORNELISSE, [No Value]

VARESCO, L

VASEN, H

WIJNEN, J

Unknown

Texas A&amp;M Repository

Yell Leaders & Yell Practice - 72

University of Groningen Research Database

7 NEW MUTATIONS IN HMSH2, AN HNPCC GENE, IDENTIFIED BY DENATURING GRADIENT-GEL ELECTROPHORESIS

Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common autosomal dominant cancer-susceptibility condition. The recent isolation of the DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) responsible for HNPCC has allowed the search for germ-line mutations in affected individuals. In this study we used denaturing gradient-gel electrophoresis to screen for mutations in the hMSH2 gene. Analysis of all the 16 exons of hMSH2, in 34 unrelated HNPCC kindreds, has revealed seven novel pathogenic germ-line mutations resulting in stop codons either directly or through frameshifts. Additionally, nucleotide substitutions giving rise to one missense, two silent, and one useful polymorphism have been identified. The proportion of families in which hMSH2 mutations were found is 21%. Although the spectrum of mutations spread at the hMSH2 gene among HNPCC patients appears extremely heterogeneous, we were not able to establish any correlation between the site of the individual mutations and the corresponding tumor spectrum. Our results indicate that, given the genomic size and organization of the hMSH2 gene and the heterogeneity of its mutation spectrum, a rapid and efficient mutation detection procedure is necessary for routine molecular diagnosis and presymptomatic detection of the disease in a clinical setup

NARCIS 

Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common autosomal dominant cancer-susceptibility condition. The recent isolation of the DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) responsible for HNPCC has allowed the search for germ-line mutations in affected individuals. In this study we used denaturing gradient-gel electrophoresis to screen for mutations in the hMSH2 gene. Analysis of all the 16 exons of hMSH2, in 34 unrelated HNPCC kindreds, has revealed seven novel pathogenic germ-line mutations resulting in stop codons either directly or through frameshifts. Additionally, nucleotide substitutions giving rise to one missense, two silent, and one useful polymorphism have been identified. The proportion of families in which hMSH2 mutations were found is 21%. Although the spectrum of mutations spread at the hMSH2 gene among HNPCC patients appears extremely heterogeneous, we were not able to establish any correlation between the site of the individual mutations and the corresponding tumor spectrum. Our results indicate that, given the genomic size and organization of the hMSH2 gene and the heterogeneity of its mutation spectrum, a rapid and efficient mutation detection procedure is necessary for routine molecular diagnosis and presymptomatic detection of the disease in a clinical setup.</p

Dissertations of the University of Groningen

University of Groningen

Proceedings - University of Groningen

ARTS repository - University of Groningen

Yell Leaders & Yell Practice - 72

Abstract

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Full text

Available Versions

Texas A&M Repository

University of Groningen Research Database

NARCIS

Dissertations of the University of Groningen

Dissertations of the University of Groningen

University of Groningen

Proceedings - University of Groningen

Proceedings - University of Groningen

ARTS repository - University of Groningen

ARTS repository - University of Groningen

Yell Leaders & Yell Practice - 72

Abstract

Similar works

Full text

Available Versions

Texas A&amp;M Repository

University of Groningen Research Database

NARCIS

Dissertations of the University of Groningen

Dissertations of the University of Groningen

University of Groningen

Proceedings - University of Groningen

Proceedings - University of Groningen

ARTS repository - University of Groningen

ARTS repository - University of Groningen

Texas A&M Repository