Journal article
Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma
Science translational medicine, Vol.3(98), pp.98ra82-98ra82
08/31/2011
DOI: 10.1126/scitranslmed.3002409
PMID: 21885404
Abstract
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.
Details
- Title: Subtitle
- Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma
- Creators
- Munir R Tanas - Department of Molecular Genetics and Anatomic Pathology, Lerner Research Institute, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44195, USAAndrea SbonerAndre M OliveiraMichele R Erickson-JohnsonJessica HespeltPhilip J HanwrightJohn FlanaganYuling LuoKerry FenwickRachael NatrajanCostas MitsopoulosMarketa ZvelebilBenjamin L HochSharon W WeissMaria Debiec-RychterRaf SciotRob B WestAlexander J LazarAlan AshworthJorge S Reis-FilhoChristopher J LordMark B GersteinMark A RubinBrian P Rubin
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.3(98), pp.98ra82-98ra82
- Publisher
- United States
- DOI
- 10.1126/scitranslmed.3002409
- PMID
- 21885404
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Grant note
- BREAST CANCER NOW RESEARCH CENTRE / Breast Cancer Now UL1 RR024989 / NCRR NIH HHS
- Language
- English
- Date published
- 08/31/2011
- Academic Unit
- Pathology
- Record Identifier
- 9984047722102771
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