The cytogenetics of<unk>  gave some of the first clues of an underlying genetic alteration. A balanced, reciprocal translocation t(1;3)(p36.3;q25) in<unk>  tumor cells was first described by Mendlick et al. in 2001 (). This led to the landmark paper by Tanas et al. in 2011() describing the specific genes involved in the translocation associated with the most common forms of<unk> . This alteration results in the fusion of genes coding for two transcription co-activators (transcriptional regulators): TAZ (transcriptional co-activator with PDZ-binding motif) also known as WWTR1 (WW domain-containing transcription regulator protein 1) and CAMTA1 (calmodulin-binding transcription activator 1). The names in parenthesis are not relevant to casual (or even science) readers but are included to help distinguish them from other genes. For instance, another gene with an entirely different function, Tafazzin, is unrelated to<unk>  but confusingly, also referred to as TAZ. In any case, the<unk>  translocation results in an abnormal ‘fusion gene’ that expresses an abnormal mRNA resulting in synthesis of a fusion protein variant of TAZ that is always turned on. This form of TAZ always resides in the nucleus and therefore is constitutively active. It binds and turns on a very important member of the TEAD family of transcription factors and this causes cells to proliferate. It is this production of the TAZ-TEAD transcriptome that causes the affected endothelial cells to grow into tumors. In normal cells, TAZ is considered a major negative transducer of the Hippo pathway, a signaling system that regulates organ size by causing cells to stop growing when they touch each other (contact inhibition). Many upstream inputs regulate the Hippo signal which normally functions to turn off or de-activate TAZ by keeping it in the cytoplasm and out of the nucleus. In<unk>  cells, the abnormal fusion TAZ is ‘immune’ to this input and just stays in the nucleus, and continuing to stimulate cell growth. Note that about 10% of<unk>  patients harbor a different translocation. This one similarly results in the constitutive activation of YAP, an orthologue of TAZ (i.e., a gene that has sequence and function that are very similar to TAZ). This also results in persistent, unregulated growth of the affected cells and therefore causes<unk> -type tumors.
Epithelioid hemangioendothelioma
Hemangioendothelioma
Mesothelioma
Epithelioid sarcoma
Alveolar soft part sarcoma
Inflammatory myofibroblastic tumour
Giant-cell reticulohistiocytoma
Reticulohistiocytoma