{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:11:45Z","timestamp":1790687505729,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012353","name":"Deutschen Konsortium f\u00fcr Translationale Krebsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012353","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Perivascular epithelioid cell tumors (PEComas) form a family of rare mesenchymal neoplasms that typically display myomelanocytic differentiation. Upregulation of mTOR signaling due the inactivation of <jats:italic>TSC1\/2 (Tuberous Sclerosis 1 and 2)<\/jats:italic> is believed to be a key oncogenic driver in this disease<jats:italic>.<\/jats:italic> Recently, a subgroup of PEComas harboring <jats:italic>TFE3<\/jats:italic> (<jats:italic>Transcription Factor E3<\/jats:italic>) rearrangements and presenting with a distinctive morphology has been identified. <jats:italic>TSC1\/2<\/jats:italic> and <jats:italic>TFE3<\/jats:italic> aberrations are deemed to be mutually exclusive in PEComa, with two different pathogenic mechanisms assumed to lead to tumorigenesis. Here, we challenge this dichotomy by presenting a case of a clinically aggressive <jats:italic>TCS1<\/jats:italic>\u2010mutated PEComa displaying a <jats:italic>TFE3<\/jats:italic>\u2010altered phenotype. FISH analysis was suggestive of a <jats:italic>TFE3<\/jats:italic> inversion; however, RNA and whole genome sequencing was ultimately unable to identify a fusion involving the gene. However, a copy number increase of the chromosomal region encompassing <jats:italic>TFE3<\/jats:italic> was detected and transcriptome analysis confirmed upregulation of <jats:italic>TFE3,<\/jats:italic> which was also seen at the protein level. Therefore, we believe that the TSC1\/2\u2010mTOR pathway and TFE3 overexpression can simultaneously contribute to tumorigenesis in PEComa. Our comprehensive genetic analyses add to the understanding of the complex pathogenic mechanisms underlying PEComa and harbor insights for clinical treatment options.<\/jats:p>","DOI":"10.1002\/cjp2.187","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T13:17:20Z","timestamp":1605187040000},"page":"3-9","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["<scp>TFE3<\/scp> activation in a <scp><i>TSC1<\/i>\u2010altered<\/scp> malignant <scp>PEComa<\/scp>: challenging the dichotomy of the underlying pathogenic mechanisms"],"prefix":"10.1002","volume":"7","author":[{"given":"Maren","family":"Schmiester","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology, and Tumor Immunology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"},{"name":"Berlin Institute of Health (BIH)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Dolnik","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Tumor Immunology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Kornak","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"},{"name":"Institute of Human Genetics University Medical Center G\u00f6ttingen  G\u00f6ttingen 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Medical Genetics and Human Genetics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Brakemeier","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Urology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin 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