Research ArticleCancer

Identification of a Disease-Defining Gene Fusion in Epithelioid Hemangioendothelioma

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Science Translational Medicine  31 Aug 2011:
Vol. 3, Issue 98, pp. 98ra82
DOI: 10.1126/scitranslmed.3002409

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Integrating transcriptomic sequencing with conventional cytogenetics, we identified WWTR1 (WW domain–containing transcription regulator 1) (3q25) and CAMTA1 (calmodulin-binding transcription activator 1) (1p36) as the two genes involved in the t(1;3)(p36;q25) chromosomal translocation that is characteristic of epithelioid hemangioendothelioma (EHE), a vascular sarcoma. This WWTR1/CAMTA1 gene fusion is under the transcriptional control of the WWTR1 promoter and encodes a putative chimeric transcription factor that joins the amino terminus of WWTR1, a protein that is highly expressed in endothelial cells, in-frame to the carboxyl terminus of CAMTA1, a protein that is normally expressed only in brain. Thus, CAMTA1 expression is activated inappropriately through a promoter-switch mechanism. The gene fusion is present in virtually all EHEs tested but is absent from all other vascular neoplasms, demonstrating it to be a disease-defining genetic alteration. A sensitive and specific break-apart fluorescence in situ hybridization assay was also developed to detect the translocation and will assist in the evaluation of this diagnostically challenging neoplasm. The chimeric WWTR1/CAMTA1 transcription factor may represent a therapeutic target for EHE and offers the opportunity to shed light on the functions of two poorly characterized proteins.


  • Citation: M. R. Tanas, A. Sboner, A. M. Oliveira, M. R. Erickson-Johnson, J. Hespelt, P. J. Hanwright, J. Flanagan, Y. Luo, K. Fenwick, R. Natrajan, C. Mitsopoulos, M. Zvelebil, B. L. Hoch, S. W. Weiss, M. Debiec-Rychter, R. Sciot, R. B. West, A. J. Lazar, A. Ashworth, J. S. Reis-Filho, C. J. Lord, M. B. Gerstein, M. A. Rubin, B. P. Rubin, Identification of a Disease-Defining Gene Fusion in Epithelioid Hemangioendothelioma. Sci. Transl. Med. 3, 98ra82 (2011).

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