The Initiative Funds a Research Study on Epithelioid Hemangioendothelioma

December 15, 2011: The Liddy Shriver Sarcoma Initiative is pleased to announce the funding of a $50,000 research grant, "Mechanism of transformation by WWTR1/CAMTA1 fusion protein in epithelioid hemangioendothelioma." The study is being conducted by Brian Rubin, MD, PhD, in the Anatomic Pathology/Molecular Genetics Department at the Cleveland Clinic’s Lerner Research Institute. This grant was funded, in part, by a generous donation of $10,000 from the Center for Research and Analysis of Vascular Tumors (CRAVAT).

Dr. Rubin said:

"Epithelioid hemangioendothelioma (EHE) is a rare vascular (endothelial cell) sarcoma that can arise in soft tissue, bone, and parenchymal organs such as liver and lung and is characterized by a t(1;3)(p36;q25) translocation. Treatment is surgical; there is no approved/standardized medical treatment. Disease-specific mortality ranges from 13-18% for EHE arising in soft tissue and is 40% and 65% for EHE that arises in lung and liver respectively."

He and his colleagues have identified WWTR1 and CAMTA1 as the genes that are fused by the t(1;3)(p36;q25) translocation in EHE. He noted:

"We have shown that WWTR1-CAMTA1 gene fusion is disease-defining; it was present in 87% of EHE (N=47) while it was not found in 26 other types (118 total cases) of other vascular tumors. The gene fusion encodes a putative chimeric transcription factor. We hypothesize that WWTR1/CAMTA1 transforms an endothelial cell/endothelial cell precursor through aberrant expression of a neural specific transcriptional program. We predict this is mediated by the CAMTA1 portion of the fusion protein that is ectopically and markedly overexpressed in endothelial cells via the strong endothelial promoter donated by the WWTR1 gene; a so-called promoter switch mechanism."

The identification of the WWTR1/CAMTA1 gene fusion is a powerful finding, enabling the development of specific diagnostic tests for EHE and novel, molecular-based studies to elucidate the mechanism of WWTR1/CAMTA1 transformation.

Dr. Rubin has set up three specific aims for the study:

  1. Develop CAMTA1 immunohistochemical bioassay for diagnosis of EHE.
  2. Determine the oncogenic cellular processes controlled by WWTR1/CAMTA1.
  3. Determine the transcriptional targets of WWTR1/CAMTA1.

He told us that, “Overall, successful completion of these studies will result in the development of an easy-to-use diagnostic test for EHE diagnosis and provide significant insight into understanding the precise molecular mechanism(s) of WWTR1/CAMTA1 transformation, which could be translated into targeted therapy for treatment of EHE.”

Read more in the experimental plan for this study which appears in the December 2011 issue of ESUN.


V8N6 ESUN Copyright © 2011 Liddy Shriver Sarcoma Initiative.