Extrachromosomal driver mutations in glioblastoma and low-grade glioma

Sergey Nikolaev (), Federico Santoni (), Marco Garieri, Periklis Makrythanasis, Emilie Falconnet, Michel Guipponi, Anne Vannier, Ivan Radovanovic, Frederique Bena, Françoise Forestier, Karl Schaller, Valerie Dutoit, Virginie Clement-Schatlo, Pierre-Yves Dietrich and Stylianos E. Antonarakis ()
Additional contact information
Sergey Nikolaev: University of Geneva Medical School
Federico Santoni: University of Geneva Medical School
Marco Garieri: University of Geneva Medical School
Periklis Makrythanasis: University of Geneva Medical School
Emilie Falconnet: University of Geneva Medical School
Michel Guipponi: Geneva University Hospitals—HUG, Service of Genetic Medicine
Anne Vannier: Geneva University Hospitals—HUG, Service of Genetic Medicine
Ivan Radovanovic: University of Geneva Medical School
Frederique Bena: Geneva University Hospitals—HUG, Service of Genetic Medicine
Françoise Forestier: Geneva University Hospitals—HUG, Service of Genetic Medicine
Karl Schaller: University of Geneva Medical School
Valerie Dutoit: Center of Oncology, Geneva University Hospitals—HUG
Virginie Clement-Schatlo: University of Geneva Medical School
Pierre-Yves Dietrich: Center of Oncology, Geneva University Hospitals—HUG
Stylianos E. Antonarakis: University of Geneva Medical School

Nature Communications, 2014, vol. 5, issue 1, 1-7

Abstract: Abstract Alteration of the number of copies of double minutes (DMs) with oncogenic EGFR mutations in response to tyrosine kinase inhibitors is a novel adaptive mechanism of glioblastoma. Here we provide evidence that such mutations in DMs, called here amplification-linked extrachromosomal mutations (ALEMs), originate extrachromosomally and could therefore be completely eliminated from the cancer cells. By exome sequencing of seven glioblastoma patients we reveal ALEMs in EGFR, PDGFRA and other genes. These mutations together with DMs are lost by cancer cells in culture. We confirm the extrachromosomal origin of such mutations by showing that wild-type and mutated DMs may coexist in the same tumour. Analysis of 4,198 tumours suggests the presence of ALEMs across different tumour types with the highest prevalence in glioblastomas and low-grade gliomas. The extrachromosomal nature of ALEMs explains the observed drastic changes in the amounts of mutated oncogenes (like EGFR or PDGFRA) in glioblastoma in response to environmental changes.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms6690 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6690

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6690

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().