Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.

dc.contributor.author

Killela, Patrick J

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Pirozzi, Christopher J

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Healy, Patrick

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Reitman, Zachary J

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Lipp, Eric

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Rasheed, B Ahmed

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Yang, Rui

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Diplas, Bill H

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Wang, Zhaohui

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Greer, Paula K

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Zhu, Huishan

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Wang, Catherine Y

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Carpenter, Austin B

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Friedman, Henry

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Friedman, Allan H

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Keir, Stephen T

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He, Jie

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He, Yiping

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McLendon, Roger E

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Herndon, James E

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Yan, Hai

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Bigner, Darell D

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United States

dc.date.accessioned

2018-03-01T14:21:53Z

dc.date.available

2018-03-01T14:21:53Z

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2014-03-30

dc.description.abstract

Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival.

dc.identifier

https://www.ncbi.nlm.nih.gov/pubmed/24722048

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1765

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1949-2553

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https://hdl.handle.net/10161/16105

dc.language

eng

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Impact Journals, LLC

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Oncotarget

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10.18632/oncotarget.1765

dc.subject

Adult

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Biomarkers, Tumor

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Female

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Glioma

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Humans

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Isocitrate Dehydrogenase

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Male

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Middle Aged

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Mutation

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Neoplasm Grading

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Prognosis

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Promoter Regions, Genetic

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Survival Rate

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Telomerase

dc.title

Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.

dc.type

Journal article

duke.contributor.orcid

Reitman, Zachary J|0000-0002-9122-9550

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Diplas, Bill H|0000-0001-9248-7351

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Friedman, Henry|0000-0001-7588-032X

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McLendon, Roger E|0000-0001-6682-4588

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Yan, Hai|0000-0001-9509-8431

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Bigner, Darell D|0000-0001-5548-4899

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/24722048

pubs.begin-page

1515

pubs.end-page

1525

pubs.issue

6

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Basic Science Departments

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Biostatistics & Bioinformatics

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Faculty

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Institutes and Centers

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Medicine

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Medicine, Medical Oncology

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Neurosurgery

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Pathology

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Pediatrics

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Pharmacology & Cancer Biology

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School of Medicine

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Student

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Surgery

pubs.publication-status

Published

pubs.volume

5

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