The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
ABSTRACT Diffuse astrocytoma and glioblastoma (GBM) constitute a group of diffusely infiltrating astrocytic neoplasms, which more commonly arise in cerebral hemispheres of adults. The prevalence of malignant transformation of diffuse astrocytoma to anaplastic astrocytoma and GBM varies from 40% to 7...
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| Format: | Article |
| Language: | English |
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Sociedade Brasileira de Patologia Clínica
2017-10-01
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| Series: | Jornal Brasileiro de Patologia e Medicina Laboratorial |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1676-24442017000500338&tlng=en |
| _version_ | 1818975413563555840 |
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| author | Eduardo Cambruzzi |
| author_facet | Eduardo Cambruzzi |
| author_sort | Eduardo Cambruzzi |
| collection | DOAJ |
| description | ABSTRACT Diffuse astrocytoma and glioblastoma (GBM) constitute a group of diffusely infiltrating astrocytic neoplasms, which more commonly arise in cerebral hemispheres of adults. The prevalence of malignant transformation of diffuse astrocytoma to anaplastic astrocytoma and GBM varies from 40% to 75% of cases in different series. Distinct genetic abnormalities are related to neoplastic progression, and the cells prone to glial neoplasm development include progenitor cells, stem cells, or differentiated cells. Primary GBM arises typically de novo, with no previous history of a lower-grade precursor lesion. Secondary GBM evolves from low-grade astrocytoma, is predominant in younger patients, and frequently exhibits isocitrate dehydrogenase (IDH) 1 and 2 mutations. IDH1/2 mutated gliomas have been associated with a better prognosis when compared to IDH-wildtype gliomas. IDH mutations are rare in primary GBM and gliomas arising in children. Evidence suggests that IDH mutations lead to a hypermethylation phenotype and represent early events in tumoral transformation of the central nervous system (CNS) due to the production of the oncometabolite 2-hydroxyglutarate. IDH1 mutations precede tumor protein p53 (TP53) mutations in around 63% of cases of diffuse astrocytomas, and result in loss in 10q and 19q chromosomes. Primary GBMs are also associated with alterations in cell proliferation [epidermal growth fator receptor (EGFR) amplification/mutation, platelet derived growth factor receptor alpha (PDGFRA) amplifications, neurofibromin 1 (NF1) mutations], abnormal apoptotic index [cyclin dependent kinase inhibitor 2A (CDKN2A) homozygous deletion and TP53 mutation], and aberrant progression in G1/S phase of the cell cycle. |
| first_indexed | 2024-12-20T15:55:34Z |
| format | Article |
| id | doaj.art-342226e0898b438492fd99e7608c6c09 |
| institution | Directory Open Access Journal |
| issn | 1678-4774 |
| language | English |
| last_indexed | 2024-12-20T15:55:34Z |
| publishDate | 2017-10-01 |
| publisher | Sociedade Brasileira de Patologia Clínica |
| record_format | Article |
| series | Jornal Brasileiro de Patologia e Medicina Laboratorial |
| spelling | doaj.art-342226e0898b438492fd99e7608c6c092022-12-21T19:34:28ZengSociedade Brasileira de Patologia ClínicaJornal Brasileiro de Patologia e Medicina Laboratorial1678-47742017-10-0153533834410.5935/1676-2444.20170055The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomasEduardo CambruzziABSTRACT Diffuse astrocytoma and glioblastoma (GBM) constitute a group of diffusely infiltrating astrocytic neoplasms, which more commonly arise in cerebral hemispheres of adults. The prevalence of malignant transformation of diffuse astrocytoma to anaplastic astrocytoma and GBM varies from 40% to 75% of cases in different series. Distinct genetic abnormalities are related to neoplastic progression, and the cells prone to glial neoplasm development include progenitor cells, stem cells, or differentiated cells. Primary GBM arises typically de novo, with no previous history of a lower-grade precursor lesion. Secondary GBM evolves from low-grade astrocytoma, is predominant in younger patients, and frequently exhibits isocitrate dehydrogenase (IDH) 1 and 2 mutations. IDH1/2 mutated gliomas have been associated with a better prognosis when compared to IDH-wildtype gliomas. IDH mutations are rare in primary GBM and gliomas arising in children. Evidence suggests that IDH mutations lead to a hypermethylation phenotype and represent early events in tumoral transformation of the central nervous system (CNS) due to the production of the oncometabolite 2-hydroxyglutarate. IDH1 mutations precede tumor protein p53 (TP53) mutations in around 63% of cases of diffuse astrocytomas, and result in loss in 10q and 19q chromosomes. Primary GBMs are also associated with alterations in cell proliferation [epidermal growth fator receptor (EGFR) amplification/mutation, platelet derived growth factor receptor alpha (PDGFRA) amplifications, neurofibromin 1 (NF1) mutations], abnormal apoptotic index [cyclin dependent kinase inhibitor 2A (CDKN2A) homozygous deletion and TP53 mutation], and aberrant progression in G1/S phase of the cell cycle.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1676-24442017000500338&tlng=enastrocytomaglioblastomaisocitrate dehydrogenasepathologyprognosisbrain |
| spellingShingle | Eduardo Cambruzzi The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas Jornal Brasileiro de Patologia e Medicina Laboratorial astrocytoma glioblastoma isocitrate dehydrogenase pathology prognosis brain |
| title | The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas |
| title_full | The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas |
| title_fullStr | The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas |
| title_full_unstemmed | The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas |
| title_short | The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas |
| title_sort | role of idh1 2 mutations in the pathogenesis of secondary glioblastomas |
| topic | astrocytoma glioblastoma isocitrate dehydrogenase pathology prognosis brain |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1676-24442017000500338&tlng=en |
| work_keys_str_mv | AT eduardocambruzzi theroleofidh12mutationsinthepathogenesisofsecondaryglioblastomas AT eduardocambruzzi roleofidh12mutationsinthepathogenesisofsecondaryglioblastomas |