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Title:
Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities | Acta Neuropathologica
Description:
IDH wild type (IDHwt) anaplastic astrocytomas WHO grade III (AA III) are associated with poor outcome. To address the possibilities of molecular subsets among astrocytoma or of diagnostic reclassification, we analyzed a series of 160 adult IDHwt tumors comprising 120 AA III and 40 diffuse astrocytomas WHO grade II (A II) for molecular hallmark alterations and established methylation and copy number profiles. Based on molecular profiles and hallmark alterations the tumors could be grouped into four major sets. 124/160 (78 %) tumors were diagnosed as the molecular equivalent of conventional glioblastoma (GBM), and 15/160 (9 %) as GBM-H3F3A mutated (GBM-H3). 13/160 (8 %) exhibited a distinct methylation profile that was most similar to GBM-H3-K27, however, lacked the H3F3A mutation. This group was enriched for tumors of infratentorial and midline localization and showed a trend towards a more favorable prognosis. All but one of the 120 IDHwt AA III could be assigned to these three groups. 7 tumors recruited from the 40 A II, comprised a variety of molecular signatures and all but one were reclassified into distinct WHO entities of lower grades. Interestingly, TERT mutations were exclusively restricted to the molecular GBM (78 %) and associated with poor clinical outcome. However, the GBM-H3 group lacking TERT mutations appeared to fare even worse. Our data demonstrate that most of the tumors diagnosed as IDHwt astrocytomas can be allocated to other tumor entities on a molecular basis. The diagnosis of IDHwt diffuse astrocytoma or anaplastic astrocytoma should be used with caution.
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article, pubmed, google, scholar, idh, cas, cancer, germany, acta, heidelberg, neuropathol, german, mutations, gliomas, university, research, molecular, tumors, central, department, center, astrocytomas, david, dktk, neuropathology, supplementary, capper, diffuse, glioblastoma, classification, brain, institute, material, analysis, adult, tumor, reuss, sahm, andreas, deimling, idhwt, grade, astrocytoma, mutation, neurology, consortium, dkfz, hospital, privacy, cookies,
Topics {✒️}
month download article/chapter christel herold-mende copy-number profiling identify joerg-christian tonn andreas von deimling neuropathology—haarlem consensus guidelines central nervous system idh mutant diffuse biologically relevant groups german cancer consortium full article pdf partner site essen/düsseldorf tert promoter mutations diffuse lower-grade gliomas grade ii/iii gliomas melanie bewerunge-hudler poor clinical outcome german cancer net idh mutation status idh-mutated astrocytomas common adult gliomas university medical center privacy choices/manage cookies idh1-r132h immunohistochemistry andreas unterberg author information authors program sys-glio michael platten brain tumor immunology copy number profiles gbm-h3f3a mutated von deimling gbm-h3-k27 idhwt diffuse astrocytoma unfavorable prognostic effect 1p19q codeleted gliomas idh1 mutated glioblastomas european economic area michael weller integrative genomic analysis alfaro-munoz kd integrated genomic analysis van thuijl hf chromatin remodelling genes parsons dw maria fernanda ruiz proteomics core facility sigmund-freud strasse 25 nhs foundation trust human glioblastoma multiforme
Questions {❓}
- Horbinski C (2013) What do we know about IDH1/2 mutations so far, and how do we use it?
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headline:Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities
description:
IDH wild type (IDHwt) anaplastic astrocytomas WHO grade III (AA III) are associated with poor outcome. To address the possibilities of molecular subsets among astrocytoma or of diagnostic reclassification, we analyzed a series of 160 adult IDHwt tumors comprising 120 AA III and 40 diffuse astrocytomas WHO grade II (A II) for molecular hallmark alterations and established methylation and copy number profiles. Based on molecular profiles and hallmark alterations the tumors could be grouped into four major sets. 124/160 (78 %) tumors were diagnosed as the molecular equivalent of conventional glioblastoma (GBM), and 15/160 (9 %) as GBM-H3F3A mutated (GBM-H3). 13/160 (8 %) exhibited a distinct methylation profile that was most similar to GBM-H3-K27, however, lacked the H3F3A mutation. This group was enriched for tumors of infratentorial and midline localization and showed a trend towards a more favorable prognosis. All but one of the 120 IDHwt AA III could be assigned to these three groups. 7 tumors recruited from the 40 A II, comprised a variety of molecular signatures and all but one were reclassified into distinct WHO entities of lower grades. Interestingly, TERT mutations were exclusively restricted to the molecular GBM (78 %) and associated with poor clinical outcome. However, the GBM-H3 group lacking TERT mutations appeared to fare even worse. Our data demonstrate that most of the tumors diagnosed as IDHwt astrocytomas can be allocated to other tumor entities on a molecular basis. The diagnosis of IDHwt diffuse astrocytoma or anaplastic astrocytoma should be used with caution.
datePublished:2015-06-19T00:00:00Z
dateModified:2015-06-19T00:00:00Z
pageStart:407
pageEnd:417
sameAs:https://doi.org/10.1007/s00401-015-1454-8
keywords:
IDH1
IDH2
Astrocytoma
Glioblastoma
Classification
TERT
H3F3A
Pathology
Neurosciences
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headline:Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities
description:
IDH wild type (IDHwt) anaplastic astrocytomas WHO grade III (AA III) are associated with poor outcome. To address the possibilities of molecular subsets among astrocytoma or of diagnostic reclassification, we analyzed a series of 160 adult IDHwt tumors comprising 120 AA III and 40 diffuse astrocytomas WHO grade II (A II) for molecular hallmark alterations and established methylation and copy number profiles. Based on molecular profiles and hallmark alterations the tumors could be grouped into four major sets. 124/160 (78 %) tumors were diagnosed as the molecular equivalent of conventional glioblastoma (GBM), and 15/160 (9 %) as GBM-H3F3A mutated (GBM-H3). 13/160 (8 %) exhibited a distinct methylation profile that was most similar to GBM-H3-K27, however, lacked the H3F3A mutation. This group was enriched for tumors of infratentorial and midline localization and showed a trend towards a more favorable prognosis. All but one of the 120 IDHwt AA III could be assigned to these three groups. 7 tumors recruited from the 40 A II, comprised a variety of molecular signatures and all but one were reclassified into distinct WHO entities of lower grades. Interestingly, TERT mutations were exclusively restricted to the molecular GBM (78 %) and associated with poor clinical outcome. However, the GBM-H3 group lacking TERT mutations appeared to fare even worse. Our data demonstrate that most of the tumors diagnosed as IDHwt astrocytomas can be allocated to other tumor entities on a molecular basis. The diagnosis of IDHwt diffuse astrocytoma or anaplastic astrocytoma should be used with caution.
datePublished:2015-06-19T00:00:00Z
dateModified:2015-06-19T00:00:00Z
pageStart:407
pageEnd:417
sameAs:https://doi.org/10.1007/s00401-015-1454-8
keywords:
IDH1
IDH2
Astrocytoma
Glioblastoma
Classification
TERT
H3F3A
Pathology
Neurosciences
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