{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:43:53Z","timestamp":1787028233727,"version":"build-2736575974"},"reference-count":20,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy. Methods: This was a multicenter study conducted at five sites within the US. The data were collected from 1 January 2004 to 31 January 2021. We conducted a retrospective analysis to identify PEComa patients with next-generation sequencing (NGS) data and compared outcomes based on mutations. Results: No significant differences in survival were identified between TSC-1 and TSC-2 mutated PEComa or TSC-1\/-2 versus other mutations. No significant difference was seen in progression-free survival (PFS) after first-line therapy between mTOR inhibition versus other systemic therapies. Conclusions: We were unable to detect differences in survival based on genomic alterations or PFS between mTOR inhibition versus other systemic therapies. Future studies should seek to identify other drivers of TSC-1\/-2 silencing that could predict response to mTOR inhibition.<\/jats:p>","DOI":"10.3390\/genes13111932","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T06:37:45Z","timestamp":1666593465000},"page":"1932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Impact of TSC-1 and -2 Mutations on Response to Therapy in Malignant PEComa: A Multicenter Retrospective Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-7739","authenticated-orcid":false,"given":"Lawrence","family":"Liu","sequence":"first","affiliation":[{"name":"City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Dehner","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Grandhi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lyu","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8849-2139","authenticated-orcid":false,"given":"Dana C.","family":"Borcherding","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S. A.","family":"Chrisinger","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqin","family":"Luo","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tao","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Parkes","sequence":"additional","affiliation":[{"name":"Carbone Cancer Center, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam Q.","family":"Bui","sequence":"additional","affiliation":[{"name":"Stanford Cancer Institute, Stanford University, Palo Alto, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Davis","sequence":"additional","affiliation":[{"name":"Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed M.","family":"Milhem","sequence":"additional","affiliation":[{"name":"Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52722, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1185-5448","authenticated-orcid":false,"given":"Varun","family":"Monga","sequence":"additional","affiliation":[{"name":"Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52722, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Weiss","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4572-6668","authenticated-orcid":false,"given":"Brian Van","family":"Tine","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1719-0771","authenticated-orcid":false,"given":"Angela C.","family":"Hirbe","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/cup.13061","article-title":"Malignant PEComa","volume":"45","author":"Haiges","year":"2018","journal-title":"J. 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