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Oncogene Mutation Survey in MPNST Cell Lines Enhances the Dominant Role of Hyperactive Ras in NF1 Associated Pro-Survival and Malignancy

Malignant peripheral nerve sheath tumors (MPNST) are a type of soft tissue sarcoma that can be associated with germline mutations in Neurofibromatosis type 1 (NF1) or may occur sporadically. Although the etiology of MPNST is poorly understood, it is clear that a loss of function of the NF1 gene, enc...

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Detalles Bibliográficos
Autores principales: Sun, Daochun, Tainsky, Michael A., Haddad, Ramsi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Libertas Academica 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273949/
https://www.ncbi.nlm.nih.gov/pubmed/22346343
http://dx.doi.org/10.4137/TOG.S8830
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author Sun, Daochun
Tainsky, Michael A.
Haddad, Ramsi
author_facet Sun, Daochun
Tainsky, Michael A.
Haddad, Ramsi
author_sort Sun, Daochun
collection PubMed
description Malignant peripheral nerve sheath tumors (MPNST) are a type of soft tissue sarcoma that can be associated with germline mutations in Neurofibromatosis type 1 (NF1) or may occur sporadically. Although the etiology of MPNST is poorly understood, it is clear that a loss of function of the NF1 gene, encoding a Ras-GAP, is an important factor in the tumorigenesis of the inherited form of MPNST. Tumor latency in NF1 patients suggests that additional mutational events are probably required for malignancy. In order to define oncogene mutations associated with 5 MPNST cell lines, we assayed the 238 most frequent mutations in 19 commonly activated oncogenes using mass spectroscopy-based analysis. All 238 mutation sites in the assayed oncogenes were determined to harbor only wild-type sequences. These data suggest that hyperactive Ras resulting from the loss function of neurofibromin may be sufficient to set up the direction of malignant transformation of Schwann cells to MPNST.
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spelling pubmed-32739492012-02-16 Oncogene Mutation Survey in MPNST Cell Lines Enhances the Dominant Role of Hyperactive Ras in NF1 Associated Pro-Survival and Malignancy Sun, Daochun Tainsky, Michael A. Haddad, Ramsi Transl Oncogenomics Short Report Malignant peripheral nerve sheath tumors (MPNST) are a type of soft tissue sarcoma that can be associated with germline mutations in Neurofibromatosis type 1 (NF1) or may occur sporadically. Although the etiology of MPNST is poorly understood, it is clear that a loss of function of the NF1 gene, encoding a Ras-GAP, is an important factor in the tumorigenesis of the inherited form of MPNST. Tumor latency in NF1 patients suggests that additional mutational events are probably required for malignancy. In order to define oncogene mutations associated with 5 MPNST cell lines, we assayed the 238 most frequent mutations in 19 commonly activated oncogenes using mass spectroscopy-based analysis. All 238 mutation sites in the assayed oncogenes were determined to harbor only wild-type sequences. These data suggest that hyperactive Ras resulting from the loss function of neurofibromin may be sufficient to set up the direction of malignant transformation of Schwann cells to MPNST. Libertas Academica 2012-01-18 /pmc/articles/PMC3273949/ /pubmed/22346343 http://dx.doi.org/10.4137/TOG.S8830 Text en © the author(s), publisher and licensee Libertas Academica Ltd. This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.
spellingShingle Short Report
Sun, Daochun
Tainsky, Michael A.
Haddad, Ramsi
Oncogene Mutation Survey in MPNST Cell Lines Enhances the Dominant Role of Hyperactive Ras in NF1 Associated Pro-Survival and Malignancy
title Oncogene Mutation Survey in MPNST Cell Lines Enhances the Dominant Role of Hyperactive Ras in NF1 Associated Pro-Survival and Malignancy
title_full Oncogene Mutation Survey in MPNST Cell Lines Enhances the Dominant Role of Hyperactive Ras in NF1 Associated Pro-Survival and Malignancy
title_fullStr Oncogene Mutation Survey in MPNST Cell Lines Enhances the Dominant Role of Hyperactive Ras in NF1 Associated Pro-Survival and Malignancy
title_full_unstemmed Oncogene Mutation Survey in MPNST Cell Lines Enhances the Dominant Role of Hyperactive Ras in NF1 Associated Pro-Survival and Malignancy
title_short Oncogene Mutation Survey in MPNST Cell Lines Enhances the Dominant Role of Hyperactive Ras in NF1 Associated Pro-Survival and Malignancy
title_sort oncogene mutation survey in mpnst cell lines enhances the dominant role of hyperactive ras in nf1 associated pro-survival and malignancy
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273949/
https://www.ncbi.nlm.nih.gov/pubmed/22346343
http://dx.doi.org/10.4137/TOG.S8830
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