Effective therapeutic intervention and comprehensive genetic analysis of mTOR signaling in PEComa: A case report

Fleur Weeber, Marco J. Koudijs, Marlous Hoogstraat, Nicolle J M Besselink, Stef Van Lieshout, Isaac J. Nijman, Edwin Cuppen, G. Johan Offerhaus, Emile E. Voest

Research output: Contribution to journalArticle

Abstract

Background/Aim: 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. Materials and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)3399-3403
Number of pages5
JournalAnticancer Research
Volume35
Issue number6
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Perivascular Epithelioid Cell Neoplasms
Genetic Engineering
Sirolimus
Comparative Genomic Hybridization
Immunohistochemistry
Therapeutics
Neoplasms
Polyploidy
Karyotype
Genome
Mutation
Genes

Keywords

  • Case report
  • Everolimus
  • Mesenchymal neoplasm
  • mTOR inhibition
  • PEC
  • PEC tumor
  • PEComa
  • Targeted therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Weeber, F., Koudijs, M. J., Hoogstraat, M., Besselink, N. J. M., Van Lieshout, S., Nijman, I. J., ... Voest, E. E. (2015). Effective therapeutic intervention and comprehensive genetic analysis of mTOR signaling in PEComa: A case report. Anticancer Research, 35(6), 3399-3403.

Effective therapeutic intervention and comprehensive genetic analysis of mTOR signaling in PEComa : A case report. / Weeber, Fleur; Koudijs, Marco J.; Hoogstraat, Marlous; Besselink, Nicolle J M; Van Lieshout, Stef; Nijman, Isaac J.; Cuppen, Edwin; Offerhaus, G. Johan; Voest, Emile E.

In: Anticancer Research, Vol. 35, No. 6, 01.06.2015, p. 3399-3403.

Research output: Contribution to journalArticle

Weeber, F, Koudijs, MJ, Hoogstraat, M, Besselink, NJM, Van Lieshout, S, Nijman, IJ, Cuppen, E, Offerhaus, GJ & Voest, EE 2015, 'Effective therapeutic intervention and comprehensive genetic analysis of mTOR signaling in PEComa: A case report', Anticancer Research, vol. 35, no. 6, pp. 3399-3403.
Weeber F, Koudijs MJ, Hoogstraat M, Besselink NJM, Van Lieshout S, Nijman IJ et al. Effective therapeutic intervention and comprehensive genetic analysis of mTOR signaling in PEComa: A case report. Anticancer Research. 2015 Jun 1;35(6):3399-3403.
Weeber, Fleur ; Koudijs, Marco J. ; Hoogstraat, Marlous ; Besselink, Nicolle J M ; Van Lieshout, Stef ; Nijman, Isaac J. ; Cuppen, Edwin ; Offerhaus, G. Johan ; Voest, Emile E. / Effective therapeutic intervention and comprehensive genetic analysis of mTOR signaling in PEComa : A case report. In: Anticancer Research. 2015 ; Vol. 35, No. 6. pp. 3399-3403.
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