Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

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

Purificacion Estevez-Garcia12, Angel Castaño3, Ana C Martin4, Fernando Lopez-Rios5, Joaquin Iglesias4, Sandra Muñoz-Galván1, Iker Lopez-Calderero12, Sonia Molina-Pinelo1, Maria D Pastor1, Amancio Carnero1, Luis Paz-Ares12 and Rocio Garcia-Carbonero12*

Author affiliations

1 Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain

2 Medical Oncology Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain

3 Pathology Department, Hospital de Fuenlabrada, Madrid, Spain

4 Bionostra Aplicaciones Biotecnológicas, S.L.U., Madrid, Spain

5 Pathology Department, Centro Integral Oncológico Clara Campal, Madrid, Spain

For all author emails, please log on.

Citation and License

BMC Cancer 2012, 12:514  doi:10.1186/1471-2407-12-514

Published: 12 November 2012

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 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.

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 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).

Conclusions

PDGFRβ 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.

Keywords:
VEGFR; PDGFR; SNP; Colorectal cancer; Angiogenesis; Prognosis