Novel YAP1‐TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Issue 8 (5th June 2013)

• Record Type: Journal Article
• Authors: Antonescu, Cristina R.; Le, Francois; Mosquera, Juan‐Miguel; Sboner, Andrea; Zhang, Lei; Chen, Chun‐Liang; Chen, Hsiao‐Wei; Pathan, Nursat; Krausz, Thomas; Dickson, Brendan C.; Weinreb, Ilan; Rubin, Mark A.; Hameed, Meera; Fletcher, Christopher D. M.
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 8(2013:Aug.)
• Page Start: 775
• Page End: 784
• Publication Date: 2013-06-05
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22073
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Conventional epithelioid hemangioendotheliomas (EHE) have a distinctive morphologic appearance and are characterized by a recurrent t(1;3) translocation, resulting in a <italic>WWTR1‐CAMTA1</italic> 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 <italic>TFE3</italic> gene rearrangement was applied to the index case as well as to nine additional cases, selected through negative <italic>WWTR1‐CAMTA1</italic> screening. A control group, including 18 epithelioid hemangiomas, nine pseudomyogenic HE, and three epithelioid angiosarcomas, was also tested. <italic>TFE3</italic> 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 <italic>YAP1‐TFE3</italic> fusion was thus detected, which was further validated by FISH and reverse transcription polymerase chain reaction (RT‐PCR). <italic>YAP1</italic> gene rearrangements were then confirmed in seven of the remaining nine <italic>TFE3</italic>‐rearranged EHEs by FISH. No <italic>TFE3</italic> structural abnormalities were detected in any of the controls. The <italic>TFE3</italic>‐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 <italic>YAP1‐TFE3</italic> fusions. © 2013 Wiley Periodicals, Inc.</p> </abstract>