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VEGFA gene locus analysis across 80 human tumour types reveals gene amplification in several neoplastic entities

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Abstract

Background

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.

Aims

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).

Results

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.

Conclusion

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.

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Acknowledgments

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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Authors and Affiliations

  1. Molecular Pathology Unit, Institute of Pathology, University Hospital of Basel, Schonbeinstrasse 40, 4003, Basel, Switzerland

    Mariacarla Andreozzi, Luca Quagliata, Joel R. Gsponer, Christian Ruiz, Serenella Eppenberger-Castori, Luigi Tornillo & Luigi M. Terracciano

  2. Oncotest GmbH, Freiburg, Germany

    Vincent Vuaroqueaux

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  1. Mariacarla Andreozzi
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  2. Luca Quagliata
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  3. Joel R. Gsponer
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  4. Christian Ruiz
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  5. Vincent Vuaroqueaux
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  6. Serenella Eppenberger-Castori
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  7. Luigi Tornillo
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  8. Luigi M. Terracciano
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Corresponding author

Correspondence to Luigi M. Terracciano.

Electronic supplementary material

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10456_2013_9396_MOESM1_ESM.tif

Supplementary Table 1. Rates of VEGFA gene locus amplification in the analysed tumour types as evaluated using FISH, extended version (TIFF 1924 kb)

10456_2013_9396_MOESM2_ESM.tif

Supplementary Table 2. Rates of VEGFA gene locus amplification using the alternative cut off criterion in selected tumour types as evaluated using FISH (TIFF 1068 kb)

10456_2013_9396_MOESM3_ESM.tif

Supplementary Table 3. Rates of VEGFA gene locus amplification using the alternative cut off criterion in the analysed tumour types as evaluated using FISH, extended version (TIFF 4245 kb)

10456_2013_9396_MOESM4_ESM.tif

Supplementary Table 4. Rates of VEGFA gene locus amplification in human analysed tumour xenografts as evaluated by FISH, extended version (TIFF 1744 kb)

10456_2013_9396_MOESM5_ESM.tif

Supplementary Table 5. Rates of VEGFA gene locus amplification in human selected tumour xenografts using the alternative cut off criterion as evaluated by FISH (TIFF 692 kb)

10456_2013_9396_MOESM6_ESM.tif

Supplementary Table 6. Rates of VEGFA gene locus amplification in human tumour xenografts using the alternative cut off criterion as evaluated by FISH (TIFF 885 kb)

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Andreozzi, M., Quagliata, L., Gsponer, J.R. et al. VEGFA gene locus analysis across 80 human tumour types reveals gene amplification in several neoplastic entities. Angiogenesis 17, 519–527 (2014). https://doi.org/10.1007/s10456-013-9396-z

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  • DOI: https://doi.org/10.1007/s10456-013-9396-z

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