A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites

Errani, C., Zhang, L., Sung, Y. S., Hajdu, M., Singer, S., Maki, R. G., Healey, J. H., Antonescu, C. R. (August 2011) A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer, 50 (8). pp. 644-53. ISSN 1098-2264 (Electronic)1045-2257 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/21584898
DOI: 10.1002/gcc.20886


The classification of epithelioid vascular tumors remains challenging, as there is considerable morphological overlap between tumor subtypes, across the spectrum from benign to malignant categories. A t(1;3)(p36.3;q25) translocation was reported in two cases of epithelioid hemangioendothelioma (EHE), however, no follow-up studies have been performed to identify the gene fusion or to assess its prevalence in a larger cohort of patients. We undertook a systematic molecular analysis of 17 EHE, characterized by classic morphological and immunophenotypic features, from various anatomical locations and with different malignant potential. For comparison, we analyzed 13 epithelioid hemangiomas, five epithelioid angiosarcomas, and four epithelioid sarcoma-like EHE. A fluorescence in situ hybridization (FISH) positional cloning strategy, spanning the cytogenetically defined regions on chromosomes 1p36.3 and 3q25, confirmed rearrangements in two candidate genes from these loci in all EHE cases tested. None of the other benign or malignant epithelioid vascular tumors examined demonstrated these abnormalities. Subsequent reverse transcription-polymerase chain reaction (RT-PCR) confirmed in three EHE the WWTR1-CAMTA1 fusion product. CAMTA1 and WWTR1 have been previously shown to play important roles in oncogenesis. Our results demonstrate the presence of a WWTR1-CAMTA1 fusion in all EHE tested from bone, soft tissue, and visceral location (liver, lung) in keeping with a unique and specific pathological entity. Thus, FISH or RT-PCR analysis for the presence of WWTR1-CAMTA1 fusion may serve as a useful molecular diagnostic tool in challenging diagnoses.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Calcium-Binding Proteins/*genetics Female *Gene Fusion Hemangioendothelioma, Epithelioid/diagnosis/*genetics Humans In Situ Hybridization, Fluorescence Intracellular Signaling Peptides and Proteins/*genetics Male Middle Aged Oncogene Proteins, Fusion/genetics Trans-Activators/*genetics Translocation, Genetic
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: August 2011
Date Deposited: 21 Oct 2016 19:36
Last Modified: 21 Oct 2016 19:36
PMCID: PMC3264678
Related URLs:
URI: https://repository.cshl.edu/id/eprint/33718

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