Cargando…
Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1
Neurofibromatosis type-1 (NF1), resulting from NF1 gene loss of function, is characterized by an increased risk of developing benign and malignant peripheral nerve sheath tumors (MPNSTs). Whereas the cellular heterogeneity of NF1-associated tumors has been well studied, the molecular heterogeneity o...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500234/ https://www.ncbi.nlm.nih.gov/pubmed/23244685 http://dx.doi.org/10.1186/1479-7364-6-18 |
_version_ | 1782250081346387968 |
---|---|
author | Thomas, Laura Mautner, Victor-Felix Cooper, David N Upadhyaya, Meena |
author_facet | Thomas, Laura Mautner, Victor-Felix Cooper, David N Upadhyaya, Meena |
author_sort | Thomas, Laura |
collection | PubMed |
description | Neurofibromatosis type-1 (NF1), resulting from NF1 gene loss of function, is characterized by an increased risk of developing benign and malignant peripheral nerve sheath tumors (MPNSTs). Whereas the cellular heterogeneity of NF1-associated tumors has been well studied, the molecular heterogeneity of MPNSTs is still poorly understood. Mutational heterogeneity within these malignant tumors greatly complicates the study of the underlying mechanisms of tumorigenesis. We have explored this molecular heterogeneity by performing loss of heterozygosity (LOH) analysis of the NF1, TP53, RB1, PTEN, and CDKN2A genes on sections of 10 MPNSTs derived from 10 unrelated NF1 patients. LOH data for the TP53 gene was found to correlate with the results of p53 immunohistochemical analysis in the same tumor sections. Further, approximately 70% of MPNSTs were found to display intra-tumoral molecular heterogeneity as evidenced by differences in the level of LOH between different sections of the same tumor samples. This study constitutes the first systematic analysis of molecular heterogeneity within MPNSTs derived from NF1 patients. Appreciation of the existence of molecular heterogeneity in NF1-associated tumors is important not only for optimizing somatic mutation detection, but also for understanding the mechanisms of NF1 tumorigenesis, a prerequisite for the development of specifically targeted cancer therapeutics. |
format | Online Article Text |
id | pubmed-3500234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35002342012-11-17 Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 Thomas, Laura Mautner, Victor-Felix Cooper, David N Upadhyaya, Meena Hum Genomics Primary Research Neurofibromatosis type-1 (NF1), resulting from NF1 gene loss of function, is characterized by an increased risk of developing benign and malignant peripheral nerve sheath tumors (MPNSTs). Whereas the cellular heterogeneity of NF1-associated tumors has been well studied, the molecular heterogeneity of MPNSTs is still poorly understood. Mutational heterogeneity within these malignant tumors greatly complicates the study of the underlying mechanisms of tumorigenesis. We have explored this molecular heterogeneity by performing loss of heterozygosity (LOH) analysis of the NF1, TP53, RB1, PTEN, and CDKN2A genes on sections of 10 MPNSTs derived from 10 unrelated NF1 patients. LOH data for the TP53 gene was found to correlate with the results of p53 immunohistochemical analysis in the same tumor sections. Further, approximately 70% of MPNSTs were found to display intra-tumoral molecular heterogeneity as evidenced by differences in the level of LOH between different sections of the same tumor samples. This study constitutes the first systematic analysis of molecular heterogeneity within MPNSTs derived from NF1 patients. Appreciation of the existence of molecular heterogeneity in NF1-associated tumors is important not only for optimizing somatic mutation detection, but also for understanding the mechanisms of NF1 tumorigenesis, a prerequisite for the development of specifically targeted cancer therapeutics. BioMed Central 2012-09-04 /pmc/articles/PMC3500234/ /pubmed/23244685 http://dx.doi.org/10.1186/1479-7364-6-18 Text en Copyright ©2012 Thomas et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Primary Research Thomas, Laura Mautner, Victor-Felix Cooper, David N Upadhyaya, Meena Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 |
title | Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 |
title_full | Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 |
title_fullStr | Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 |
title_full_unstemmed | Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 |
title_short | Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 |
title_sort | molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500234/ https://www.ncbi.nlm.nih.gov/pubmed/23244685 http://dx.doi.org/10.1186/1479-7364-6-18 |
work_keys_str_mv | AT thomaslaura molecularheterogeneityinmalignantperipheralnervesheathtumorsassociatedwithneurofibromatosistype1 AT mautnervictorfelix molecularheterogeneityinmalignantperipheralnervesheathtumorsassociatedwithneurofibromatosistype1 AT cooperdavidn molecularheterogeneityinmalignantperipheralnervesheathtumorsassociatedwithneurofibromatosistype1 AT upadhyayameena molecularheterogeneityinmalignantperipheralnervesheathtumorsassociatedwithneurofibromatosistype1 |