Skip to Main content Skip to Navigation
Journal articles

Whole genome duplication is an early event leading to aneuploidy in IDH-wild type glioblastoma

Abstract : Glioblastoma, the most frequent and lethal form of glioma, displays chromosome instability and recurrent somatic copy number alterations (SCNA). Chromothripsis and whole genome duplication (WGD) have been recently identified in cancer. In the present study, we analyzed SCNA and determine the ploidy pattern in 123 IDH-wild-type glioblastomas, using SNP array data. WGD and chromothripsis events were validated using, respectively, FISH and CTLPScanner. WGD was detected in 11.4% glioblastomas (14/123) and was associated with TP53 mutation (p = 0.0068). It was an early event occurring after the recurrent SCNA observed in diffuse high-grade gliomas. Glioblastomas with WGD were more aneuploid compared to glioblastomas without WGD (p < 0.0001). Chromothripsis occurred in 29.3% glioblastomas (36/123) and mostly affected chromosomes 7, 9 and 12, with amplification of oncogenes (EGFR, MDM2/CDK4), and homozygous deletion of tumor suppressor genes (CDKN2A). There was a significant association between chromothripsis and gene rearrangement at a given locus. WGD is an early genetic event significantly associated to TP53 mutation and leading to chromosome instability and aneuploidy in IDH-wild-type glioblastoma. Chromothripsis recurrently targets oncogenes and tumor suppressor genes that are key players in gliomagenesis and tumor progression. The occurrence of chromothripsis points to underlying gene rearrangements (including gene fusions), potential therapeutic targets in glioblastoma.
Document type :
Journal articles
Complete list of metadata

Cited literature [38 references]  Display  Hide  Download
Contributor : Elizabeth Bernardo Connect in order to contact the contributor
Submitted on : Wednesday, December 19, 2018 - 10:29:11 AM
Last modification on : Wednesday, April 27, 2022 - 4:43:00 AM
Long-term archiving on: : Wednesday, March 20, 2019 - 2:26:22 PM


GLIAD 08-WGD-chrom (Boisselier...
Publisher files allowed on an open archive



Blandine Boisselier, Frédéric Dugay, Marc-Antoine Belaud-Rotureau, Anne Coutolleau, Emmanuel Garcion, et al.. Whole genome duplication is an early event leading to aneuploidy in IDH-wild type glioblastoma. Oncotarget, Impact journals, 2018, 9 (89), pp.36017-36028. ⟨10.18632/oncotarget.26330⟩. ⟨inserm-01960034⟩



Record views


Files downloads