PhD Scientific Days 2023

Pathology I.

ATRX-deficient IDH-wildtype adult high-grade gliomas display novel, clinically relevant genetic patterns by comprehensive genomic profiling

Előadó neve

Dr. Bedics, Gábor

Neptun code

XA7QBG

Előadó munkahelye

Department of Pathology and Experimental Cancer Research

Előadó telefonszáma

+36304371071

Előadó e-mail címe

bedics.gabor@med.semmelweis-univ.hu

Az előadás címe

ATRX-deficient IDH-wildtype adult high-grade gliomas display novel, clinically relevant genetic patterns by comprehensive genomic profiling

Szerző(k) neve és munkahelye

Gábor Bedics1,2, Péter Szőke1, Bence Bátai1,2, Tibor Nagy1,2, Gergő Papp1, Noémi Kránitz3, Hajnalka Rajnai1, Lilla Reiniger1, Csaba Bödör1,2, Bálint Scheich1

1Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
3Department of Pathology, County Hospital Győr, Petz Aladár Hospital, Győr

Bemutatás módja

Szóbeli

Szekció

Pathology I.

Language of the presentation

Hungarian

Preferred session

Pathology and Oncology

Összefoglaló szövege

Glioblastomas are the most common IDH-wildtype adult high-grade gliomas, frequently harboring mutations in the promoter region of the TERT gene (pTERT) and utilizing the subsequent telomerase overexpression for telomere length maintenance. However, some rare cases show loss of ATRX and use alternative lengthening of telomeres.

We aimed to perform the first complex genetic analysis specifically concentrating on the latter subgroup, since the molecular properties including potential clinically relevant features are poorly characterized.

Comprehensive genomic profiling (CGP) of 12 ATRX-deficient and 13 ATRX-intact IDH-wildtype adult high-grade gliomas was performed using the Illumina TruSight Oncology 500 targeted next-generation sequencing panel.

There was no significant difference regarding the main clinical characteristics of the examined groups. ATRX and pTERT mutations were revealed to be mutually exclusive by the CGP. DNMT3A alterations were confined to ATRX-deficient, while PTEN mutations to ATRX-intact cases. EGFR amplification was relatively rare, while alterations of the RAS-MAPK pathway, including NF1 mutations and BRAF alterations, were more characteristic in the ATRX-deficient group. Several pathogenic or likely pathogenic variants of genes related to homologous recombination repair were detected in both groups, but with different patterns of affected genes. Two ATRX-deficient tumors with high tumor mutational burden and mismatch repair deficiency were found. One of these showed a peculiar association of oligodendroglioma-like morphology, novel fusions involving the NTRK2 and LRRFIP2 genes, POLE mutations as well as therapy-induced MLH1 and PMS2 loss. The other showed loss of MSH2 and MSH6 without genetic alterations in the encoding genes suggesting an epigenetic background.

Apparent, statistically significant differences in the genetic characteristics of ATRX-deficient and ATRX-intact IDH-wildtype adult high-grade gliomas were revealed by our studies. These observations suggest that tumors from the former group are particularly intriguing targets of potential future therapeutic interventions including immunotherapies combined with MAPK pathway inhibition as well as DNA-repair inhibitors.

This work was funded by the EU's Horizon 2020 Research and Innovation Program under grant agreement No. 739593, by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA-24 and TKP2021-NVA-11 funding schemes, by the Semmelweis 250+ Stipendium, as well as the ÚNKP-22-3-II New National Excellence Program of the Ministry for Culture and Innovation from the National Research, Development and Innovation Fund.

University and Doctoral School

Semmelweis University, Doctoral School of Pathological Sciences

Supervisor

Dr. Csaba Bödör

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4694

Start

09:30

End

09:45

Authors (legacy)

Gábor Bedics1,2, Péter Szőke1, Bence Bátai1,2, Tibor Nagy1,2, Gergő Papp1, Noémi Kránitz3, Hajnalka Rajnai1, Lilla Reiniger1, Csaba Bödör1,2, Bálint Scheich1

1Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
3Department of Pathology, County Hospital Győr, Petz Aladár Hospital, Győr