Diffuse astrocytoma, AYA-type, frequently MAPK-altered: report of 45 patients

A putative molecular subtype of IDH-wildtype diffuse glioma with recurrent MAPK pathway alterations has recently been reported. By dimensionality reduction analysis of genome-wide methylation profiling, these tumors form a distinct methylation cluster of gliomas. Characterization of 47 tumors from 45 patients reveals that these gliomas are predominantly supratentorial in young adults, are highly infiltrative, and harbor mitogen-activated protein kinase (MAPK) pathway alterations with high rates of CDKN2A/2B deletion, PDGFRA amplification, MYCN amplification, NF1 variants, and BRAF alterations. The tumors' epigenetics are distinct from other adult and pediatric gliomas in the 2021 World Health Organization (WHO) classification. The histology of the gliomas most often demonstrates high-grade astrocytic features, but can be variable from tumor to tumor, as well as fall into a spectrum of histologic grades. Outcomes show considerable variability based on histologic grade and molecular features, supporting grading within this group of tumors to ensure optimal care choices on an individual patient basis. These unifying epigenetic, sequencing, and infiltrative astrocytic features allow the tumors to be considered diffuse astrocytoma, adolescent, and young adult-type, with MAPK alterations (DAYA).

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Publication Details

Journal
Acta Neuropathologica
Published
2025-04-09
DOI
https://doi.org/10.1007/s00401-025-02873-8
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Diffuse astrocytoma, AYA-type, frequently MAPK-altered: report of 45 patients

John M. Skaugen, Maria A. Gubbiotti, Omkar Singh, Robert Macaulay et al.
Acta Neuropathologica
Glioma Diagnosis and Treatment
article

Diffuse astrocytoma, AYA-type, frequently MAPK-altered: report of 45 patients

John M. Skaugen, Maria A. Gubbiotti, Omkar Singh, Robert Macaulay, Caterina Giannini, J. Stephen Nix, Orwa Aboud, Daniel F. Marker, Scott Kulich, Patrick J. Cimino, Qinwen Mao, Ewa Borys, Stewart G. Neill, Peter Pytel, Christopher H. Dampier, Zied Abdullaev, Nishant Tiwari, MacLean P. Nasrallah, Arie Perry, Mouied Alashari, Kyle Conway, Jeong Han Lee, Jeffrey Helgager, Kenneth Aldape, Karen Dazelle, Martha Quezado, Daniel Brown, Hye‐Jung Chung, Cheddhi Thomas, Sandra Camelo‐Piragua, John Newman, Igor Lima Fernandes, Laila Naqib-Osman
article en

Abstract

A putative molecular subtype of IDH-wildtype diffuse glioma with recurrent MAPK pathway alterations has recently been reported. By dimensionality reduction analysis of genome-wide methylation profiling, these tumors form a distinct methylation cluster of gliomas. Characterization of 47 tumors from 45 patients reveals that these gliomas are predominantly supratentorial in young adults, are highly infiltrative, and harbor mitogen-activated protein kinase (MAPK) pathway alterations with high rates of CDKN2A/2B deletion, PDGFRA amplification, MYCN amplification, NF1 variants, and BRAF alterations. The tumors' epigenetics are distinct from other adult and pediatric gliomas in the 2021 World Health Organization (WHO) classification. The histology of the gliomas most often demonstrates high-grade astrocytic features, but can be variable from tumor to tumor, as well as fall into a spectrum of histologic grades. Outcomes show considerable variability based on histologic grade and molecular features, supporting grading within this group of tumors to ensure optimal care choices on an individual patient basis. These unifying epigenetic, sequencing, and infiltrative astrocytic features allow the tumors to be considered diffuse astrocytoma, adolescent, and young adult-type, with MAPK alterations (DAYA).

Acta NeuropathologicaVol. 149(1)
National Institutes of Health (US), Walmart (United States) (US), The University of Texas MD Anderson Cancer Center (US), University of Wisconsin–Madison (US), Emory University (US), University of Pittsburgh (US), University of California, San Francisco (US), Loyola University Chicago (US), University of Utah (US), University of Michigan (US), Inova Fairfax Hospital (US), Moffitt Cancer Center (US), University of Chicago (US), Laboratório Bacchi (BR), National Institute of Neurological Disorders and Stroke (US), Ennetix (United States) (US), Phoenix Children's Hospital (US), Mayo Clinic in Arizona (US), National Cancer Institute (US), Center for Cancer Research (US), Neurological Surgery (US), University of California Davis Medical Center (US), Lower Columbia College (US), University of California, Davis (US), University of Bologna (IT), Stanford University (US)
National Institutes of Health, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 90%
Glioma Diagnosis and Treatment
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