PDGFRα/β and VEGFR2 polymorphisms in colorectal cancer: incidence and implications in clinical outcome

BMC Cancer

Research Article

Ana C Martin¹  Joaquin Iglesias¹  Sonia Molina-Pinelo²  Sandra Muñoz-Galván²  Maria D Pastor²  Amancio Carnero²  Purificacion Estevez-Garcia³  Rocio Garcia-Carbonero³  Luis Paz-Ares³  Iker Lopez-Calderero³  Fernando Lopez-Rios⁴  Angel Castaño⁵ 

[1] Bionostra Aplicaciones Biotecnológicas, S.L.U, Madrid, Spain;Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain;Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain;Medical Oncology Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain;Pathology Department, Centro Integral Oncológico Clara Campal, Madrid, Spain;Pathology Department, Hospital de Fuenlabrada, Madrid, Spain;

关键词: VEGFR;    PDGFR;    SNP;    Colorectal cancer;    Angiogenesis;    Prognosis;   

DOI  :  10.1186/1471-2407-12-514

 received in 2012-06-22, accepted in 2012-10-28,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAngiogenesis 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).MethodsVEGFR2, PDGFRα and PDGFRβ 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.ResultsFour 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 PDGFRβ [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).ConclusionsPDGFRβ 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.

【 授权许可】

Unknown   
© Estevez-Garcia et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.