Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis.
BACKGROUND
Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis.


METHODS
We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features.


RESULTS
We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these "ultramutated" tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival.


CONCLUSIONS
We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments.
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
E Zeynep
EZ
Erson-Omay
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Ahmet Okay
AO
Çağlayan
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Nikolaus
N
Schultz
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Nils
N
Weinhold
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
S Bülent
SB
Omay
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Koray
K
Özduman
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Yavuz
Y
Köksal
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Jie
J
Li
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Akdes
A
Serin Harmancı
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Victoria
V
Clark
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Geneive
G
Carrión-Grant
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Jacob
J
Baranoski
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Caner
C
Çağlar
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Tanyeri
T
Barak
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Süleyman
S
Coşkun
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Burçin
B
Baran
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Doğan
D
Köse
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Jia
J
Sun
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Mehmet
M
Bakırcıoğlu
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Jennifer
J
Moliterno Günel
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
M Necmettin
MN
Pamir
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Ketu
K
Mishra-Gorur
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Kaya
K
Bilguvar
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Katsuhito
K
Yasuno
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Alexander
A
Vortmeyer
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Anita J
AJ
Huttner
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Chris
C
Sander
Department of Neurosurgery, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut (E.Z.E.-O., A.O.Ç., S.B.O., A.S.H., V.C., G.C.-G., J.B., C.Ç., T.B., S.C., B.B., M.B., J.M.G., K.M.-G., K.B., K.Y., M.G.); Department of Genetics, Yale School of Medicine, New Haven, Connecticut (K.B., M.G.); Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York (N.S., N.W., C.S.); Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey (K.O., M.N.P.); Division of Hematology and Oncology, Faculty of Medicine, Department of Pediatrics, Selçuk University, Konya, Turkey (Y.K., D.K.); Department of Pathology, Yale School of Medicine, New Haven, Connecticut (J.L., J.S., A.V., A.J.H.).
Murat
M
Günel
D000328:Adult; D001932:Brain Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D004257:DNA Polymerase II / Q000235:genetics*; D018572:Disease-Free Survival; D005910:Glioma / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D055815:Young Adult
D000075223:Poly-ADP-Ribose Binding Proteins; D004257:DNA Polymerase II; C119525:POLE protein, human
better prognosis; germline MSH6 mutation; glioblastoma; polymerase epsilon; ultramutated tumor