title: Effective Therapeutic Intervention and Comprehensive Genetic Analysis of mTOR Signaling in PEComa: A Case Report.
abstract: OBJECTIVE
  Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms. The exact genetic alterations underlying the pathophysiology of PEComas are largely unknown, although it has been shown that activation of the Mammalian target of rapamycin (mTOR) signaling pathway plays a pivotal role. Herein we describe the successful treatment of a patient with metastatic PEComa with the mTOR inhibitor everolimus and a comprehensive analysis to identify mechanisms for response.
  
  
  METHODS
  Immunohistochemistry, array comparative genomic hybridization (aCGH) and genetic analyses were performed.
  
  
  RESULTS
  Immunohistochemistry confirmed constitutive activation of mTOR. aCGH revealed a hyperdiploid karyotype affecting large regions of the genome. Next-generation sequencing did not reveal any tumor-specific mutations in mTOR-related genes.
  
  
  CONCLUSIONS
  Our results show the complexity of determining causal genetic alterations that can predict responsiveness to mTOR inhibition, even for a tumor with a complete remission to this specific treatment.
authors.affiliation: Department of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands f.weeber@nki.nl.
authors.forename: Fleur
authors.initials: F
authors.lastname: Weeber
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Koudijs
authors.affiliation: Department of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Marlous
authors.initials: M
authors.lastname: Hoogstraat
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Nicolle J M
authors.initials: NJ
authors.lastname: Besselink
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, the Netherlands.
authors.forename: Stef
authors.initials: S
authors.lastname: VAN Lieshout
authors.affiliation: Hubrecht Institute, Utrecht, The Netherlands Department of Human Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Isaac J
authors.initials: IJ
authors.lastname: Nijman
authors.affiliation: Hubrecht Institute, Utrecht, The Netherlands Department of Human Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: G Johan
authors.initials: GJ
authors.lastname: Offerhaus
authors.affiliation: Department of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
mesh_terms: D014408:Biomarkers, Tumor; D055028:Comparative Genomic Hybridization; D000068338:Everolimus; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D054973:Perivascular Epithelioid Cell Neoplasms / Q000235:genetics* / Q000473:pathology; D012074:Remission Induction; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: PEC; PEC tumor; PEComa; case report; everolimus; mTOR inhibition; mesenchymal neoplasm; targeted therapy