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Pilocytic astrocytoma: pathology, molecular mechanisms and markers

Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. They are relatively benign (WHO grade I) and have, as a group, a 10-year survival of over 90 %. Many require merely surgical removal and only very infrequently do they progress to more malignant gliomas. Wh...

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Autores principales: Collins, V. Peter, Jones, David T. W., Giannini, Caterina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436848/
https://www.ncbi.nlm.nih.gov/pubmed/25792358
http://dx.doi.org/10.1007/s00401-015-1410-7
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author Collins, V. Peter
Jones, David T. W.
Giannini, Caterina
author_facet Collins, V. Peter
Jones, David T. W.
Giannini, Caterina
author_sort Collins, V. Peter
collection PubMed
description Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. They are relatively benign (WHO grade I) and have, as a group, a 10-year survival of over 90 %. Many require merely surgical removal and only very infrequently do they progress to more malignant gliomas. While most show classical morphology, they may present a spectrum of morphological patterns, and there are difficult cases that show similarities to other gliomas, some of which are malignant and require aggressive treatment. Until recently, almost nothing was known about the molecular mechanisms involved in their development. The use of high-throughput sequencing techniques interrogating the whole genome has shown that single abnormalities of the mitogen-activating protein kinase (MAPK) pathway are exclusively found in almost all cases, indicating that PA represents a one-pathway disease. The most common mechanism is a tandem duplication of a ≈2 Mb-fragment of #7q, giving rise to a fusion between two genes, resulting in a transforming fusion protein, consisting of the N-terminus of KIAA1549 and the kinase domain of BRAF. Additional infrequent fusion partners have been identified, along with other abnormalities of the MAP-K pathway, affecting tyrosine kinase growth factor receptors at the cell surface (e.g., FGFR1) as well as BRAF V600E, KRAS, and NF1 mutations among others. However, while the KIAA1549-BRAF fusion occurs in all areas, the incidence of the various other mutations identified differs in PAs that develop in different regions of the brain. Unfortunately, from a diagnostic standpoint, almost all mutations found have been reported in other brain tumor types, although some retain considerable utility. These molecular abnormalities will be reviewed, and the difficulties in their potential use in supporting a diagnosis of PA, when the histopathological findings are equivocal or in the choice of individualized therapy, will be discussed.
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spelling pubmed-44368482015-05-22 Pilocytic astrocytoma: pathology, molecular mechanisms and markers Collins, V. Peter Jones, David T. W. Giannini, Caterina Acta Neuropathol Review Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. They are relatively benign (WHO grade I) and have, as a group, a 10-year survival of over 90 %. Many require merely surgical removal and only very infrequently do they progress to more malignant gliomas. While most show classical morphology, they may present a spectrum of morphological patterns, and there are difficult cases that show similarities to other gliomas, some of which are malignant and require aggressive treatment. Until recently, almost nothing was known about the molecular mechanisms involved in their development. The use of high-throughput sequencing techniques interrogating the whole genome has shown that single abnormalities of the mitogen-activating protein kinase (MAPK) pathway are exclusively found in almost all cases, indicating that PA represents a one-pathway disease. The most common mechanism is a tandem duplication of a ≈2 Mb-fragment of #7q, giving rise to a fusion between two genes, resulting in a transforming fusion protein, consisting of the N-terminus of KIAA1549 and the kinase domain of BRAF. Additional infrequent fusion partners have been identified, along with other abnormalities of the MAP-K pathway, affecting tyrosine kinase growth factor receptors at the cell surface (e.g., FGFR1) as well as BRAF V600E, KRAS, and NF1 mutations among others. However, while the KIAA1549-BRAF fusion occurs in all areas, the incidence of the various other mutations identified differs in PAs that develop in different regions of the brain. Unfortunately, from a diagnostic standpoint, almost all mutations found have been reported in other brain tumor types, although some retain considerable utility. These molecular abnormalities will be reviewed, and the difficulties in their potential use in supporting a diagnosis of PA, when the histopathological findings are equivocal or in the choice of individualized therapy, will be discussed. Springer Berlin Heidelberg 2015-03-20 2015 /pmc/articles/PMC4436848/ /pubmed/25792358 http://dx.doi.org/10.1007/s00401-015-1410-7 Text en © The Author(s) 2015 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Review
Collins, V. Peter
Jones, David T. W.
Giannini, Caterina
Pilocytic astrocytoma: pathology, molecular mechanisms and markers
title Pilocytic astrocytoma: pathology, molecular mechanisms and markers
title_full Pilocytic astrocytoma: pathology, molecular mechanisms and markers
title_fullStr Pilocytic astrocytoma: pathology, molecular mechanisms and markers
title_full_unstemmed Pilocytic astrocytoma: pathology, molecular mechanisms and markers
title_short Pilocytic astrocytoma: pathology, molecular mechanisms and markers
title_sort pilocytic astrocytoma: pathology, molecular mechanisms and markers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436848/
https://www.ncbi.nlm.nih.gov/pubmed/25792358
http://dx.doi.org/10.1007/s00401-015-1410-7
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