Replication error in colorectal carcinoma: association with loss of heterozygosity at mismatch repair loci and clinicopathological variables.
Anticancer Res
; 19(3A): 1821-6, 1999.
Article
em En
| MEDLINE
| ID: mdl-10470121
ABSTRACT
Instability of microsatellite DNA or replication error (RER) is characteristic of tumours caused by mismatch repair (MMR) deficiency. Germline mutations in MMR genes are associated with Hereditary non-polyposis colorectal carcinoma (HNPCC) and somatic mutations in these genes are also found in a substantial fraction of colorectal cancers (CRC). In this study we concurrently screened colorectal tumours for the RER phenotype and loss of heterozygosity (LOH) at MMR gene loci. The RER phenotype was evident in 47/197 (24%) tumours. RER was more commonly detected in young patients (< 50 years) and in tumours located in the proximal colon. RER was positively associated with LOH at the hMSH2/hMSH6 loci on chromosome 2p, where LOH was observed in 46% of the RER+ tumours. LOH at hMLH1 and hPMS1 loci was more frequent in the younger patients (< 50 years). RER was not associated with clinicopathological parameters, such as Duke's stage and tumour differentiation (grade). The RER phenotype was associated with better overall survival, but there was a trend towards significance when multivariate analysis was used. This indicates that loss of MMR genes generate a less aggressive phenotype, and raises the question about RER being a useful indicator of prognosis for CRC patients.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Adenosina Trifosfatases
/
Repetições de Microssatélites
/
Perda de Heterozigosidade
/
Proteínas de Saccharomyces cerevisiae
/
Enzimas Reparadoras do DNA
/
Proteínas de Ligação a DNA
/
Reparo do DNA
/
Proteínas de Neoplasias
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
País/Região como assunto:
Europa
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Islândia