PDGFR / and VEGFR2 polymorphisms in colorectal cancer: incidence and implications in clinical outcome
| Autor: | Rocio Garcia-Carbonero, Fernando Lopez-Rios, Amancio Carnero, Sonia Molina-Pinelo, Maria Dolores Pastor, Joaquín Iglesias, A Castaño, Iker Lopez-Calderero, Ana C. Martín, Sandra Muñoz-Galván, Purificacion Estevez-Garcia, Luis Paz-Ares |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Receptor Platelet-Derived Growth Factor alpha Genotype PDGFR Angiogenesis Colorectal cancer SNP Polymorphism Single Nucleotide lcsh:RC254-282 Metastasis Receptor Platelet-Derived Growth Factor beta VEGFR Surgical oncology Cell Line Tumor Genetics medicine Humans Receptor Alleles Aged Aged 80 and over biology business.industry Incidence (epidemiology) Exons Middle Aged medicine.disease Prognosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Vascular Endothelial Growth Factor Receptor-2 Oncology Mutation Cancer research biology.protein Female Colorectal Neoplasms business HT29 Cells Platelet-derived growth factor receptor Research Article |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname BMC Cancer, Vol 12, Iss 1, p 514 (2012) BMC Cancer |
| Popis: | 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 (pG 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. This work was supported by a grant of the Ministerio de Ciencia y Tecnologia of Spain (FIT-010000-2006-45). PEG is funded by a Rio Hortega grant (09/00207) from the Instituto de Salud Carlos III (ISCiii), Ministerio de Sanidad, Spain. SMP is funded by the ISCiii (CD1100153), Fundación Científica de la Asociacion Española Contra el Cancer (AECC), Consejeria de Salud – Junta de Andalucia (PI-0224/2009) and Fundacion Mutua Madrileña (2009). MDP is funded by the ISCiii (CD0900148). LPA is funded by the ISCiii (PI081156 and PI1102688), Consejería de Innovacion, Ciencia y Empresa – Junta de Andalucia (P08-CVI-04090) and the 75th Anniversary Roche Spain Fellowship. RGC is funded by the ISCiii (PI 10.02164). |
| Databáze: | OpenAIRE |
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