PDGFRα/ß and VEGFR2 polymorphisms in colorectal cancer: incidence and implications in clinical outcome.
BMC Cancer
; 12: 514, 2012 Nov 12.
Article
em En
| MEDLINE
| ID: mdl-23146028
ABSTRACT
BACKGROUND:
Angiogenesis plays an essential role in tumor growth and metastasis, and is a major target in cancer therapy. VEGFR and PDGFR are key players involved in this process. The purpose of this study was to assess the incidence of genetic variants in these receptors and its potential clinical implications in colorectal cancer (CRC).METHODS:
VEGFR2, PDGFRα and PDGFRß mutations were evaluated by sequencing their tyrosine kinase domains in 8 CRC cell lines and in 92 samples of patients with CRC. Correlations with clinicopathological features and survival were analyzed.RESULTS:
Four SNPs were identified, three in PDGFRα [exon 12 (A12) c.1701A>G; exon 13 (A13) c.1809G>A; and exon 17 (A17) c.2439+58C>A] and one in PDGFRß [exon 19 (B19) c.2601A>G]. SNP B19, identified in 58% of tumor samples and in 4 cell lines (LS174T, LS180, SW48, COLO205), was associated with higher PDGFR and pPDGFR protein levels. Consistent with this observation, 5-year survival was greater for patients with PDGFR B19 wild type tumors (AA) than for those harboring the G-allele genotype (GA or GG) (51% vs 17%; p=0.073). Multivariate analysis confirmed SNP B19 (p=0.029) was a significant prognostic factor for survival, independent of age (p=0.060) or TNM stage (p<0.001).CONCLUSIONS:
PDGFRß exon 19 c.2601A>G SNP is commonly encountered in CRC patients and is associated with increased pathway activation and poorer survival. Implications regarding its potential influence in response to PDGFR-targeted agents remain to be elucidated.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Receptor alfa de Fator de Crescimento Derivado de Plaquetas
/
Receptor beta de Fator de Crescimento Derivado de Plaquetas
/
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
Tipo de estudo:
Incidence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
BMC Cancer
Ano de publicação:
2012
Tipo de documento:
Article