Back to Search Start Over

Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

Authors :
van Thuijl, Hinke
Scheinin, Ilari
Sie, Daoud
Alentorn, Agusti
van Essen, Hendrik
Cordes, Martijn
Fleischeuer, Ruth
Gijtenbeek, Anja
Beute, Guus
van den Brink, Wimar
Meijer, Gerrit
Havenith, Miek
Idbaih, Ahmed
Hoang-Xuan, Khê
Mokhtari, Karima
Verhaak, Roel
van der Valk, Paul
van de Wiel, Mark
Heimans, Jan
Aronica, Eleonora
Reijneveld, Jaap
Wesseling, Pieter
Ylstra, Bauke
Source :
Genome Biology; September 2014, Vol. 15 Issue: 9 p1-13, 13p
Publication Year :
2014

Abstract

The disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative of aggressive tumor behavior and can thereby complement the prognostically favorable 1p/19q co-deletion. Genome-wide, 50 base pair single-end sequencing was performed to detect CNAs in a clinically well-characterized cohort of 98 formalin-fixed paraffin-embedded low-grade gliomas. CNAs are correlated with overall survival as an endpoint. Seventy-five additional samples from spatially distinct regions and paired recurrent tumors of the discovery cohort were analyzed to interrogate the intratumoral heterogeneity and spatial evolution. Loss of 10q25.2-qter is a frequent subclonal event and significantly correlates with an unfavorable prognosis. A significant correlation is furthermore observed in a validation set of 126 and confirmation set of 184 patients. Loss of 10q25.2-qter arises in a longitudinal manner in paired recurrent tumor specimens, whereas the prognostically favorable 1p/19q co-deletion is the only CNA that is stable across spatial regions and recurrent tumors. CNAs in low-grade gliomas display extensive intratumoral heterogeneity. Distal loss of 10q is a late onset event and a marker for reduced overall survival in low-grade glioma patients. Intratumoral heterogeneity and higher frequencies of distal 10q loss in recurrences suggest this event is involved in outgrowth to the recurrent tumor.

Details

Language :
English
ISSN :
14747596 and 1474760X
Volume :
15
Issue :
9
Database :
Supplemental Index
Journal :
Genome Biology
Publication Type :
Periodical
Accession number :
ejs34078467
Full Text :
https://doi.org/10.1186/s13059-014-0471-6