Novel YAP1‐TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma
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- 5 June 2013
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 52 (8), 775-784
- https://doi.org/10.1002/gcc.22073
Abstract
Conventional epithelioid hemangioendotheliomas (EHE) have a distinctive morphologic appearance and are characterized by a recurrent t(1;3) translocation, resulting in a WWTR1‐CAMTA1 fusion gene. We have recently encountered a fusion‐negative subset characterized by a somewhat different morphology, including focally well‐formed vasoformative features, which was further investigated for recurrent genetic abnormalities. Based on a case showing strong transcription factor E3 (TFE3) immunoreactivity, fluorescence in situ hybridization (FISH) analysis for TFE3 gene rearrangement was applied to the index case as well as to nine additional cases, selected through negative WWTR1‐CAMTA1 screening. A control group, including 18 epithelioid hemangiomas, nine pseudomyogenic HE, and three epithelioid angiosarcomas, was also tested. TFE3 gene rearrangement was identified in 10 patients, with equal gender distribution and a mean age of 30 years old. The lesions were located in somatic soft tissue in six cases, lung in three and one in bone. One case with available frozen tissue was tested by RNA sequencing and FusionSeq data analysis to detect novel fusions. A YAP1‐TFE3 fusion was thus detected, which was further validated by FISH and reverse transcription polymerase chain reaction (RT‐PCR). YAP1 gene rearrangements were then confirmed in seven of the remaining nine TFE3‐rearranged EHEs by FISH. No TFE3 structural abnormalities were detected in any of the controls. The TFE3‐rearranged EHEs showed similar morphologic features with at least focally, well‐formed vascular channels, in addition to a variably solid architecture. All tumors expressed endothelial markers, as well as strong nuclear TFE3. In summary, we are reporting a novel subset of EHE occurring in young adults, showing a distinct phenotype and YAP1‐TFE3 fusions.Keywords
This publication has 27 references indexed in Scilit:
- Epithelioid Hemangioma of Bone and Soft Tissue: A Reappraisal of a Controversial EntityClinical Orthopaedics and Related Research, 2012
- A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusionNature Genetics, 2012
- Identification of a Disease-Defining Gene Fusion in Epithelioid HemangioendotheliomaScience Translational Medicine, 2011
- A novel WWTR1‐CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sitesGenes, Chromosomes and Cancer, 2011
- RSEQtools: a modular framework to analyze RNA-Seq data using compact, anonymized data summariesBioinformatics, 2010
- Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencingGenome Research, 2010
- FusionSeq: a modular framework for finding gene fusions by analyzing paired-end RNA-sequencing dataGenome Biology, 2010
- EWSR1‐POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty‐six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 geneGenes, Chromosomes and Cancer, 2010
- Expression of Yes-associated protein in common solid tumorsHuman Pathology, 2008
- A large genome center's improvements to the Illumina sequencing systemNature Methods, 2008