MSH6 mutations are frequent in hereditary nonpolyposis colorectal cancer families with normal pMSH6 expression as detected by immunohistochemistry.
Appl Immunohistochem Mol Morphol
; 20(5): 470-7, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22495361
ABSTRACT
INTRODUCTION:
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition accounting for 2% to 4% of all colorectal cancer cases worldwide. Families with germ line mutations in 1 of 6 mismatch repair genes are known as Lynch syndrome families. The largest number of mutations has been detected in the mismatch repair genes MLH1 and MSH2, but several mutations in MSH6 have also been demonstrated.AIM:
Whether HNPCC families are screened for mutations in mismatch repair genes often relies on their immunohistochemical profile. The aim of the present study was to evaluate this approach in Lynch families carrying mutations in MSH6. MATERIALS ANDMETHODS:
Results of the screening of the MSH6 gene in HNPCC families were compared with those obtained on immunohistochemical protein analysis.RESULTS:
In 56 (7%) of 815 families, at least 1 MSH6 mutation, 23 definitively pathogenic mutations and 38 missense mutations or unclassified variants, and several polymorphisms in the MSH6 gene were detected. In families carrying a pathogenic MSH6 mutation, 69.6% of 23 colon adenocarcinomas showed absence of pMSH6 in tumor tissue by immunohistochemical analysis. In 34.5%, all proteins could be detected, whereas in 34.5% pMSH6 was present and pMLH1/pPMS2 was absent.CONCLUSIONS:
If genetic screening of HNPCC families depended on immunohistochemical results, a substantial number of families harboring a pathogenic mutation in MSH6 and the vast majority of families harboring an MSH6 unclassified variant would not be detected.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Neoplasias Colorretais Hereditárias sem Polipose
/
Proteínas de Ligação a DNA
/
Mutação
Tipo de estudo:
Diagnostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Appl Immunohistochem Mol Morphol
Assunto da revista:
BIOLOGIA MOLECULAR
/
HISTOCITOQUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Dinamarca