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Individual Assignment of Adult Diffuse Gliomas into the EM/PM Molecular Subtypes Using a TaqMan Low-Density Array.

Journal article
Authors Jiuyi Li
Yang Xue
Anna Wenger
Yingyu Sun
Zheng Wang
Chuan-Bao Zhang
Yunqiu Zhang
Boglarka Fekete
Bertil Rydenhag
Asgeir Store Jakola
Tao Jiang
Helena Carén
Xiaolong Fan
Published in Clinical cancer research : an official journal of the American Association for Cancer Research
Volume 25
Issue 23
Pages 7068-7077
ISSN 1078-0432
Publication year 2019
Published at Sahlgrenska Cancer Center
Department of Laboratory Medicine
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Pages 7068-7077
Language en
Subject categories Cancer and Oncology


We aimed to develop a diagnostic platform to capture the transcriptomic resemblance of individual adult diffuse gliomas of WHO grades II-IV to neural development and the genomic signature associated with glioma progression.Based on the EM/PM classification scheme, we designed a RT-PCR-based TaqMan Low-density array (TLDA) containing 44 classifier and 4 reference genes. Samples of a training data set (GSE48865), characterized by RNA-sequencing, were utilized to optimize the TLDA design and to develop a support vector machine (SVM)-based prediction model. Complemented with Sanger sequencing for IDH1/2, and low coverage whole genome sequencing (WGS), the TLDA and SVM prediction model were tested in a validation (31 gliomas) and a test (121 gliomas) dataset.Independent of morphologically defined subtypes and grades, gliomas can be individually assigned into the EM and PM glioma subtypes with the respective areas under ROC curves at 0.86 and 0.85 in the validation dataset. The EM gliomas showed a medium overall survival (OS) of 15.6 months, whereas the medium OS for PM gliomas was not reached (hazard ratio = 3.55, 95% confidence interval: 1.96 to 6.45). The EM and PM gliomas showed distinct patterns of genomic alterations, with IDH mutation and 1p19q co-deletion in the PM gliomas and gain of chromosome 7/loss of chromosome 10 in the EM gliomas. Extensive chromosomal abnormalities marked the progression of PM gliomas.The integration of EM/PM subtyping, IDH sequencing and low coverage WGS may improve the risk stratification and selection of treatment regimens for glioma patients.

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