Genomic analysis of paired IDHwt glioblastomas reveals recurrent alterations of MPDZ at relapse after radiotherapy and chemotherapy

We aimed to identify genomic drivers of glioblastoma inevitable recurrence. Ten pairs of initial and recurrent frozen IDHwt glioblastoma samples were screened by CGH Array. Next Generation Sequencing (NGS) was then performed on an enriched cohort of 19 pairs. MPDZ alterations were analyzed using TCG...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the neurological sciences 2022-05, Vol.436, p.120207-120207, Article 120207
Main Authors: Chanez, Brice, Appay, Romain, Guille, Arnaud, Lagarde, Arnaud, Colin, Carole, Adelaide, José, Denicolai, Emilie, Jiguet-Jiglaire, Carine, Bequet, Céline, Graillon, Thomas, Boissonneau, Sébastien, Nanni-Metellus, Isabelle, Dufour, Henry, Figarella-Branger, Dominique, Chinot, Olivier, Tabouret, Emeline
Format: Article
Language:English
Subjects:
Brain Neoplasms - drug therapy
Brain Neoplasms - genetics
Brain Neoplasms - radiotherapy
Cancer
Comparative genomic hybridization array
Glioblastoma
Glioblastoma - drug therapy
Glioblastoma - genetics
Glioblastoma - radiotherapy
Glioma - genetics
Humans
Life Sciences
Membrane Proteins
Middle Aged
MPDZ
Next generation sequencing
Paired
Recurrence
Relapse
RNA, Messenger
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We aimed to identify genomic drivers of glioblastoma inevitable recurrence. Ten pairs of initial and recurrent frozen IDHwt glioblastoma samples were screened by CGH Array. Next Generation Sequencing (NGS) was then performed on an enriched cohort of 19 pairs. MPDZ alterations were analyzed using TCGA dataset. Nineteen IDHwt glioblastoma patients were included. Median age was 54.5 y/o (37.2–72.8). Using CGH array, unsupervised analysis aggregated the cohort by paired initial and recurrent tumors. Only 44% of CGH Array alterations were conserved at recurrence (amplifications: 55%; deletions: 30%). Two regions (including FPR1, 2 and 3) were lost at relapse: 19q13.33 and 19q13.41. MPDZ and 25 other genes were altered in ≥20% of recurrent tumors. NGS analysis of 29 candidate genes revealed 4 genes with pathogenic mutations: (FPR2, REL, TYRP1 and MPDZ). MPDZ (Multiple PDZ Domain Crumbs Cell Polarity Complex Component) was altered by two pathogenic mutations occurring at relapse. Using TCGA dataset we observed that a lower MPDZ mRNA expression was associated with IDHwt (p 
ISSN:0022-510X
1878-5883
DOI:10.1016/j.jns.2022.120207