PMID- 31936793
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 1
DP  - 2020 Jan 10
TI  - Contribution of mTOR and PTEN to Radioresistance in Sporadic and NF2-Associated 
      Vestibular Schwannomas: A Microarray and Pathway Analysis.
LID - 10.3390/cancers12010177 [doi]
LID - 177
AB  - The use of radiation treatment has increased for both sporadic and 
      neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS). However, 
      there are a subset of radioresistant tumors and systemic treatments that are 
      seldom used in these patients. We investigated molecular alterations after 
      radiation in three NF2-associated and five sporadically operated recurrent VS 
      after primary irradiation. We compared these findings with 49 non-irradiated (36 
      sporadic and 13 NF2-associated) VS through gene-expression profiling and pathway 
      analysis. Furthermore, we stained the key molecules of the distinct pathway by 
      immunohistochemistry. A total of 195 differentially expressed genes in sporadic 
      and NF2-related comparisons showed significant differences based on the criteria 
      of p value < 0.05 and a two-fold change. These genes were involved in pathways 
      that are known to be altered upon irradiation (e.g., mammalian target of 
      rapamycin (mTOR), phosphatase and tensin homolog (PTEN) and vascular endothelial 
      growth factor (VEGF) signaling). We observed a combined downregulation of PTEN 
      signaling and an upregulation of mTOR signaling in progressive NF2-associated VS 
      after irradiation. Immunostainings with mTOR and PTEN antibodies confirmed the 
      respective molecular alterations. Taken together, mTOR inhibition might be a 
      promising therapeutic strategy in NF2-associated VS progress after irradiation.
FAU - Gugel, Isabel
AU  - Gugel I
AD  - Center for Neuro-Oncology, Comprehensive Cancer Center Tubingen Stuttgart, 72076 
      Tubingen, Germany.
AD  - Department of Neurosurgery, University Hospital Tubingen, 72076 Tubingen, 
      Germany.
AD  - Centre of Neurofibromatosis and Rare Diseases, University Hospital Tubingen, 
      72076 Tubingen, Germany.
AD  - Interdisciplinary Division of Neuro-Oncology, University Hospital Tubingen, 72076 
      Tubingen, Germany.
AD  - Hertie Institute for Clinical Brain Research, Eberhard Karls University Tubingen, 
      72076 Tubingen, Germany.
FAU - Ebner, Florian H
AU  - Ebner FH
AD  - Department of Neurosurgery, Alfried Krupp Hospital, 45131 Essen, Germany.
FAU - Grimm, Florian
AU  - Grimm F
AD  - Center for Neuro-Oncology, Comprehensive Cancer Center Tubingen Stuttgart, 72076 
      Tubingen, Germany.
AD  - Department of Neurosurgery, University Hospital Tubingen, 72076 Tubingen, 
      Germany.
AD  - Interdisciplinary Division of Neuro-Oncology, University Hospital Tubingen, 72076 
      Tubingen, Germany.
FAU - Czemmel, Stefan
AU  - Czemmel S
AD  - Quantitative Biology Center (QBiC), University of Tubingen, 72076 Tubingen, 
      Germany.
FAU - Paulsen, Frank
AU  - Paulsen F
AD  - Center for Neuro-Oncology, Comprehensive Cancer Center Tubingen Stuttgart, 72076 
      Tubingen, Germany.
AD  - Interdisciplinary Division of Neuro-Oncology, University Hospital Tubingen, 72076 
      Tubingen, Germany.
AD  - Department of Radiation Oncology, University Hospital Tubingen, 72076 Tubingen, 
      Germany.
FAU - Hagel, Christian
AU  - Hagel C
AD  - Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20251 
      Hamburg, Germany.
FAU - Tatagiba, Marcos
AU  - Tatagiba M
AD  - Center for Neuro-Oncology, Comprehensive Cancer Center Tubingen Stuttgart, 72076 
      Tubingen, Germany.
AD  - Department of Neurosurgery, University Hospital Tubingen, 72076 Tubingen, 
      Germany.
AD  - Centre of Neurofibromatosis and Rare Diseases, University Hospital Tubingen, 
      72076 Tubingen, Germany.
AD  - Interdisciplinary Division of Neuro-Oncology, University Hospital Tubingen, 72076 
      Tubingen, Germany.
AD  - Hertie Institute for Clinical Brain Research, Eberhard Karls University Tubingen, 
      72076 Tubingen, Germany.
FAU - Nahnsen, Sven
AU  - Nahnsen S
AD  - Quantitative Biology Center (QBiC), University of Tubingen, 72076 Tubingen, 
      Germany.
FAU - Tabatabai, Ghazaleh
AU  - Tabatabai G
AD  - Center for Neuro-Oncology, Comprehensive Cancer Center Tubingen Stuttgart, 72076 
      Tubingen, Germany.
AD  - Department of Neurosurgery, University Hospital Tubingen, 72076 Tubingen, 
      Germany.
AD  - Interdisciplinary Division of Neuro-Oncology, University Hospital Tubingen, 72076 
      Tubingen, Germany.
AD  - Hertie Institute for Clinical Brain Research, Eberhard Karls University Tubingen, 
      72076 Tubingen, Germany.
LA  - eng
PT  - Journal Article
DEP - 20200110
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7016954
OTO - NOTNLM
OT  - microarray analysis
OT  - neurofibromatosis type 2
OT  - radioresistance
OT  - signaling
OT  - vestibular schwannoma
COIS- G.T. served on Advisory Boards of BMS, MSD and AbbVie; received research and/or 
      travel grants from Roche Diagnostics, Novocure and Medac; received speaker's fees 
      from Medac, Novocure. The other authors declare no conflict of interest.
EDAT- 2020/01/16 06:00
MHDA- 2020/01/16 06:01
PMCR- 2020/01/10
CRDT- 2020/01/16 06:00
PHST- 2019/12/19 00:00 [received]
PHST- 2020/01/07 00:00 [accepted]
PHST- 2020/01/16 06:00 [entrez]
PHST- 2020/01/16 06:00 [pubmed]
PHST- 2020/01/16 06:01 [medline]
PHST- 2020/01/10 00:00 [pmc-release]
AID - cancers12010177 [pii]
AID - cancers-12-00177 [pii]
AID - 10.3390/cancers12010177 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Jan 10;12(1):177. doi: 10.3390/cancers12010177.