Identification of a putative molecular subtype of adult-type diffuse astrocytoma with recurrent MAPK pathway alterations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F24%3A10482039" target="_blank" >RIV/00064203:_____/24:10482039 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/24:10482039

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KdU4zSKf1Y" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KdU4zSKf1Y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00401-024-02766-2" target="_blank" >10.1007/s00401-024-02766-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of a putative molecular subtype of adult-type diffuse astrocytoma with recurrent MAPK pathway alterations

Popis výsledku v původním jazyce

In summary, our investigation has revealed a distinct subtype of adult-type diffuse astrocytoma through DNA methylation profiling, lacking both IDH1/2 mutation or chromosome + 7/-10 signature, but characterized by recurrent alterations within the MAPK pathway and with TERT promoter mutation in 25% of these neoplasms. Given the presence of targetable gene fusions within these tumors, RNA sequencing could be of value. While DNA methylation profiling has emerged as a pivotal tool in identifying novel CNS tumors, it is evident that sole reliance on epigenetic signatures may not be adequate for establishing new tumor types. The histopathological and molecular overlap with IDH-wildtype glioblastoma indicates that recognizing these tumors as an entirely new tumor type is not justified at this stage. This also implies that currently DNA methylation profiling remains the primary method for identifying these tumors, similar to other epigenetically defined tumor types. However, the notable prevalence of targetable MAPK alterations and the slightly more favorable survival rate compared to typical IDH-wildtype glioblastomas suggest that recognizing these tumors, at least provisionally, as a molecular subtype of IDH-wildtype glioblastomas may be valuable. We suggest the term &apos;diffuse high-grade astrocytoma, MAPK pathway-altered&apos; to describe this molecular subtype of tumors. Further accumulation of cases and data is necessary to substantiate this distinction and understand the full clinical implications.

Název v anglickém jazyce

Identification of a putative molecular subtype of adult-type diffuse astrocytoma with recurrent MAPK pathway alterations

Popis výsledku anglicky

In summary, our investigation has revealed a distinct subtype of adult-type diffuse astrocytoma through DNA methylation profiling, lacking both IDH1/2 mutation or chromosome + 7/-10 signature, but characterized by recurrent alterations within the MAPK pathway and with TERT promoter mutation in 25% of these neoplasms. Given the presence of targetable gene fusions within these tumors, RNA sequencing could be of value. While DNA methylation profiling has emerged as a pivotal tool in identifying novel CNS tumors, it is evident that sole reliance on epigenetic signatures may not be adequate for establishing new tumor types. The histopathological and molecular overlap with IDH-wildtype glioblastoma indicates that recognizing these tumors as an entirely new tumor type is not justified at this stage. This also implies that currently DNA methylation profiling remains the primary method for identifying these tumors, similar to other epigenetically defined tumor types. However, the notable prevalence of targetable MAPK alterations and the slightly more favorable survival rate compared to typical IDH-wildtype glioblastomas suggest that recognizing these tumors, at least provisionally, as a molecular subtype of IDH-wildtype glioblastomas may be valuable. We suggest the term &apos;diffuse high-grade astrocytoma, MAPK pathway-altered&apos; to describe this molecular subtype of tumors. Further accumulation of cases and data is necessary to substantiate this distinction and understand the full clinical implications.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Acta Neuropathologica

ISSN

0001-6322

e-ISSN

1432-0533

Svazek periodika

148

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

5

Strana od-do

7

Kód UT WoS článku

001275268700002

EID výsledku v databázi Scopus

2-s2.0-85199040722