VEGFA gene locus analysis across 80 human tumour types reveals gene amplification in several neoplastic entities
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Angiogenesis plays a pivotal role in neoplastic growth and metastasis formation. Vascular endothelial growth factor A (VEGFA) is a major player in physiological and tumour-induced angiogenesis and numerous human tumours have been show to overexpress VEGFA. Moreover increased VEGFA gene expression has been found frequently to correlate with tumour progression, recurrences and survival. Interestingly, several studies have demonstrated that gene amplification may result in protein overexpression and that amplification of the therapeutics’ target gene can serve as an excellent predictive marker (i.e. HER2 and trastuzumab). However the impact of VEGFA gene amplification has been only recently assessed for some cancer types such as osteosarcoma, colorectal, breast and liver cancer.
This study aimed to assess VEGFA gene amplification status using fluorescent in situ hybridization (FISH) in a large cohort of different tumour entities. Thus, we investigated the incidence of VEGFA amplification using a multi-tumour tissue microarray (TMA) containing 2,837 evaluable specimens from 80 different tumour entities and 31 normal tissue types. Moreover, we validated FISH analysis as reference method to evaluate VEGFA gene status by comparing it to comparative genomic hybridization (CGH).
We observed that VEGFA locus amplification and/or polysomy represented a small but regularly detected population in several tumour entities while was not present in normal tissues. VEGFA gene alterations were predominantly observed in hepatocarcinomas, adenocarcinomas of the pancreas and intestine, large cell carcinoma of the lung and in endometrium serous carcinoma. Furthermore our data demonstrated that VEGFA detection by FISH provided highly comparable results to those generated by CGH.
Albeit with low percentage, VEGFA amplification is commonly observed across several tumour entities. Furthermore, our results demonstrated that FISH test could be used as a reliable diagnostic tool to evaluate VEGFA gene status in human specimens.
KeywordsVEGFA Gene amplification 6p12 FISH TMA
This work was supported by the Swiss National Foundation (Grant NMS1651). We would like to acknowledge Prof. Heiner Fiebig and Dr. Fred (Oncotest GmbH) for providing slides of their multi-tumour TMAs. We thank S. Schneider at the Institute of Pathology in Basel for her excellent technical support.
Conflict of interest
M.A., L.Q., J.G., C.R., S.E.C., L.T. and L.M.T. declare no competing financial interests. V.V. is employed by Oncotest GmbH.
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