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

BMC Cancer

Purificacion Estevez-Garcia²  Angel Castaño¹  Ana C Martin⁵  Fernando Lopez-Rios³  Joaquin Iglesias⁵  Sandra Muñoz-Galván⁴  Iker Lopez-Calderero²  Sonia Molina-Pinelo⁴  Maria D Pastor⁴  Amancio Carnero⁴  Luis Paz-Ares²  Rocio Garcia-Carbonero² 

[1] Pathology Department, Hospital de Fuenlabrada, Madrid, Spain

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

[3] Pathology Department, Centro Integral Oncológico Clara Campal, Madrid, Spain

[4] Instituto de Biomedicina de Sevilla (IBIS) (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain

[5] Bionostra Aplicaciones Biotecnológicas, S.L.U., Madrid, Spain

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

Others  :  1080096
DOI  :  10.1186/1471-2407-12-514

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

【 摘 要 】

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.

【 授权许可】

   
2012 Estevez-Garcia et al.; licensee BioMed Central Ltd.

【 图 表 】

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