: According to the fifth edition of the World Health Organization (WHO) Classification, diffuse gliomas typically occurring in adults are classified as oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and glioblastoma IDH-wildtype. Among these, the former has the most favorable clinical course, whereas the latter has the worst prognosis. In IDH-mutant gliomas, the IDH1 p. R132H is the most frequent IDH mutation. Other mutations in IDH1 are rare and predominantly found in astrocytomas, whereas IDH2 mutations are mostly observed in oligodendrogliomas. Astrocytomas IDH-mutant display frequent immunohistochemical loss of ATRX, which is mutually exclusive with 1p/19q codeletion. They are graded based on histopathological features and the presence of CDKN2A/B homozygous deletion, whereas the criteria for grading oligodendrogliomas are less defined. DNA methylation profiling has recently shown three additional distinct tumor types among diffuse IDH-mutant gliomas: infratentorial astrocytoma IDH mutant; primary mismatch repair deficient IDH-mutant astrocytoma (PMRDIA); and oligosarcoma. Infratentorial astrocytoma IDH-mutant is enriched in IDH1 or IDH2 mutations that differ from the IDH1 p.R132H mutation and are detectable only by gene sequencing, displays less frequent ATRX loss and MGMT promoter methylation than supratentorial IDH-mutant astrocytomas, and may additionally harbor the H3 K27M mutation, which is typically found in H3 K27-altered diffuse midline glioma. PMRDIA occurs in the context of primary mismatch repair deficiency, is characterized by frequent MSH6 mutations, hypermutation, low frequency of MGMT promoter methylation, and poor clinical outcomes. Finally, oligosarcoma is a tumor featuring oligodendroglial and sarcomatous areas, and is characterized by worse outcome and frequent 1p/19q copy number loss of heterozygosity.

IDH-mutant diffuse gliomas: tips and tricks in the era of genomic tumor classification

Ammendola, Serena;Barresi, Valeria
2023-01-01

Abstract

: According to the fifth edition of the World Health Organization (WHO) Classification, diffuse gliomas typically occurring in adults are classified as oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and glioblastoma IDH-wildtype. Among these, the former has the most favorable clinical course, whereas the latter has the worst prognosis. In IDH-mutant gliomas, the IDH1 p. R132H is the most frequent IDH mutation. Other mutations in IDH1 are rare and predominantly found in astrocytomas, whereas IDH2 mutations are mostly observed in oligodendrogliomas. Astrocytomas IDH-mutant display frequent immunohistochemical loss of ATRX, which is mutually exclusive with 1p/19q codeletion. They are graded based on histopathological features and the presence of CDKN2A/B homozygous deletion, whereas the criteria for grading oligodendrogliomas are less defined. DNA methylation profiling has recently shown three additional distinct tumor types among diffuse IDH-mutant gliomas: infratentorial astrocytoma IDH mutant; primary mismatch repair deficient IDH-mutant astrocytoma (PMRDIA); and oligosarcoma. Infratentorial astrocytoma IDH-mutant is enriched in IDH1 or IDH2 mutations that differ from the IDH1 p.R132H mutation and are detectable only by gene sequencing, displays less frequent ATRX loss and MGMT promoter methylation than supratentorial IDH-mutant astrocytomas, and may additionally harbor the H3 K27M mutation, which is typically found in H3 K27-altered diffuse midline glioma. PMRDIA occurs in the context of primary mismatch repair deficiency, is characterized by frequent MSH6 mutations, hypermutation, low frequency of MGMT promoter methylation, and poor clinical outcomes. Finally, oligosarcoma is a tumor featuring oligodendroglial and sarcomatous areas, and is characterized by worse outcome and frequent 1p/19q copy number loss of heterozygosity.
astrocytoma; oligodendroglioma; mismatch repair deficiency; oligosarcoma; IDH
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1082666
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