Low prevalence of germline hMSH6 mutations in colorectal cancer families from Spain.
World J Gastroenterol
; 11(37): 5770-6, 2005 Oct 07.
Article
em En
| MEDLINE
| ID: mdl-16270383
ABSTRACT
AIM:
To investigate the prevalence and penetrance of hMSH6 mutations in Spanish HNPCC families that was negative for mutation in hMLH1 or hMSH2.METHODS:
We used PCR-based DGGE assay and direct sequencing to screen for hMSH6 gene in 91 HNPCC families.RESULTS:
we have identified 10 families with germ-line mutations in the DNA sequence. These mutations included two intronic variation, three missense mutation, one nonsense mutation, and four silent mutations. Among the 10 germ-line mutations identified in the Spanish cohort, 8 were novel, perhaps, suggesting different mutational spectra in the Spanish population. Detailed pedigrees were constructed for the three families with a possible pathogenic hMSH6 mutation. The two silent mutations H388H and L758L, detected in a person affected of colorectal cancer at age 29, produce loss of the wild-type allele in the tumor sample. Immunohistochemical analysis showed that expression of MSH6 protein was lost only in the tumors from the carriers of V878A and Q263X mutations.CONCLUSION:
Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais Hereditárias sem Polipose
/
Testes Genéticos
/
Proteínas de Ligação a DNA
/
Mutação
Tipo de estudo:
Prevalence_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
World J Gastroenterol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Espanha