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 language | English (US) |
|---|---|
| Pages (from-to) | 3399-3403 |
| Number of pages | 5 |
| Journal | Anticancer Research |
| Volume | 35 |
| Issue number | 6 |
| State | Published - Jun 1 2015 |
| Externally published | Yes |
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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
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 journal › Article
}
TY - JOUR
T1 - Effective therapeutic intervention and comprehensive genetic analysis of mTOR signaling in PEComa
T2 - A case report
AU - Weeber, Fleur
AU - Koudijs, Marco J.
AU - Hoogstraat, Marlous
AU - Besselink, Nicolle J M
AU - Van Lieshout, Stef
AU - Nijman, Isaac J.
AU - Cuppen, Edwin
AU - Offerhaus, G. Johan
AU - Voest, Emile E.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
KW - Case report
KW - Everolimus
KW - Mesenchymal neoplasm
KW - mTOR inhibition
KW - PEC
KW - PEC tumor
KW - PEComa
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=84931360152&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84931360152&partnerID=8YFLogxK
M3 - Article
C2 - 26026101
AN - SCOPUS:84931360152
VL - 35
SP - 3399
EP - 3403
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 6
ER -