title: Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Hinke F
authors.initials: HF
authors.lastname: van Thuijl
authors.forename: Ilari
authors.initials: I
authors.lastname: Scheinin
authors.forename: Daoud
authors.initials: D
authors.lastname: Sie
authors.forename: Agusti
authors.initials: A
authors.lastname: Alentorn
authors.forename: Hendrik F
authors.initials: HF
authors.lastname: van Essen
authors.forename: Martijn
authors.initials: M
authors.lastname: Cordes
authors.forename: Ruth
authors.initials: R
authors.lastname: Fleischeuer
authors.forename: Anja M
authors.initials: AM
authors.lastname: Gijtenbeek
authors.forename: Guus
authors.initials: G
authors.lastname: Beute
authors.forename: Wimar A
authors.initials: WA
authors.lastname: van den Brink
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Miek
authors.initials: M
authors.lastname: Havenith
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.forename: Khê
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Roel Gw
authors.initials: RG
authors.lastname: Verhaak
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.forename: Mark A
authors.initials: MA
authors.lastname: van de Wiel
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Heimans
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Reijneveld
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10; D016000:Cluster Analysis; D056915:DNA Copy Number Variations; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017422:Sequence Analysis, DNA; D055815:Young Adult