Proximal and distal colorectal cancers show distinct gene-specific methylation profiles and clinical and molecular characteristics.
Eur J Cancer
; 44(9): 1290-301, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18486467
ABSTRACT
INTRODUCTION:
Accumulation of genetic and epigenetic alterations contribute to malignant transformation of normal colonic mucosa to cancer. However, the frequency and the pattern of these alterations in proximal and distal colon cancers have not been examined in detail.METHODS:
In this study, we examined methylation frequencies and patterns using 14 marker genes in 31 proximal and 43 distal colorectal cancers. We also analysed the relationship between these parameters and clinical characteristics, MSI, mutations of BRAF, KRAS and p53, LOH and global hypomethylation.RESULTS:
Three groups of tumours with varying degrees of methylation frequencies were identified very high (9%), high (22%) and low (69%) methylation. Tumours with very high and high methylation showed more frequent proximal location, MSI, BRAF mutations and less frequent LOH and global hypomethylation. The methylation markers could be classified into 3 types based on methylation frequencies, MSI status and location. Proximal tumours showed more frequent methylation of Type 2 markers, CIMP+, MSI, BRAF mutations and lower frequencies of LOH and global hypomethylation, whilst Type 3 marker, MGMT methylation was more frequently associated with distal tumours, better survival and G to A mutation in non-CpG sites in KRAS and p53 genes.CONCLUSION:
These data showed that proximal and distal colorectal cancers have distinct gene-specific methylation profiles and molecular and clinical characteristics.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Colon_e_reto
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Metilação de DNA
/
Genes Neoplásicos
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos