Copy number profiling across glioblastoma populations has implications for clinical trial design.

Abstract:

Background:Copy number alterations form prognostic molecular subtypes of glioblastoma with clear differences in median overall survival. In this study, we leverage molecular data from several glioblastoma cohorts to define the distribution of copy number subtypes across random cohorts as well as cohorts with selection biases for patients with inherently better outcome. Methods:Copy number subtype frequency was established for 4 glioblastoma patient cohorts. Two randomly selected cohorts include The Cancer Genome Atlas (TCGA) and the German Glioma Network (GGN). Two more selective cohorts include the phase II trial ARTE in elderly patients with newly diagnosed glioblastoma and a multi-institutional cohort focused on paired resected initial/recurrent glioblastoma. The paired initial/recurrent cohort also had exome data available, which allowed for evaluation of multidimensional scaling analysis. Results:Smaller selective glioblastoma cohorts are enriched for copy number subtypes that are associated with better survival, reflecting the selection of patients who do well enough to enter a clinical trial or who are deemed well enough to undergo resection at recurrence. Adding exome data to copy number data provides additional data reflective of outcome. Conclusions:The overall outcome for diffuse glioma patients is predicted by DNA structure at initial tumor resection. Molecular signature shifts across glioblastoma populations reflect the inherent bias of patient selection toward longer survival in clinical trials. Therefore it may be important to include molecular profiling, including copy number, when enrolling patients for clinical trials in order to balance arms and extrapolate relevance to the general glioblastoma population.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Cimino PJ,McFerrin L,Wirsching HG,Arora S,Bolouri H,Rabadan R,Weller M,Holland EC

doi

10.1093/neuonc/noy108

subject

Has Abstract

pub_date

2018-09-03 00:00:00

pages

1368-1373

issue

10

eissn

1522-8517

issn

1523-5866

pii

5047422

journal_volume

20

pub_type

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