Molecular subtypes of glioblastoma are relevant to lower grade glioma. Guan, X., Vengoechea, J., Zheng, S., Sloan, A. E., Chen, Y., Brat, D. J., O'Neill, B. P., de Groot, J., Yust-Katz, S., Yung, W. K., Cohen, M. L., Aldape, K. D., Rosenfeld, S., Verhaak, R. G., & Barnholtz-Sloan, J. S. PLoS One, 9(3):e91216, 2014. 1932-6203 Guan, Xiaowei Vengoechea, Jaime Zheng, Siyuan Sloan, Andrew E Chen, Yanwen Brat, Daniel J O'Neill, Brian Patrick de Groot, John Yust-Katz, Shlomit Yung, Wai-Kwan Alfred Cohen, Mark L Aldape, Kenneth D Rosenfeld, Steven Verhaak, Roeland G W Barnholtz-Sloan, Jill S P30 CA016672/CA/NCI NIH HHS/United States FP00073233/FP/OFP OASH HHS/United States P30 CA043703/CA/NCI NIH HHS/United States U24CA143883/CA/NCI NIH HHS/United States HHSN261201000057I/CA/NCI NIH HHS/United States P30 CA015083/CA/NCI NIH HHS/United States U24 CA143883/CA/NCI NIH HHS/United States HHSN261201000057C/CA/NCI NIH HHS/United States P50 CA108961/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States 2014/03/13 PLoS One. 2014 Mar 10;9(3):e91216. doi: 10.1371/journal.pone.0091216. eCollection 2014.
doi  abstract   bibtex   
BACKGROUND: Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas). METHODS: Gene expression array, single nucleotide polymorphism (SNP) array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III) from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson). Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP) was assigned using prediction models by Fine et al. RESULTS: Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs. CONCLUSIONS: GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.
@article{RN6161,
   author = {Guan, X. and Vengoechea, J. and Zheng, S. and Sloan, A. E. and Chen, Y. and Brat, D. J. and O'Neill, B. P. and de Groot, J. and Yust-Katz, S. and Yung, W. K. and Cohen, M. L. and Aldape, K. D. and Rosenfeld, S. and Verhaak, R. G. and Barnholtz-Sloan, J. S.},
   title = {Molecular subtypes of glioblastoma are relevant to lower grade glioma},
   journal = {PLoS One},
   volume = {9},
   number = {3},
   pages = {e91216},
   note = {1932-6203
Guan, Xiaowei
Vengoechea, Jaime
Zheng, Siyuan
Sloan, Andrew E
Chen, Yanwen
Brat, Daniel J
O'Neill, Brian Patrick
de Groot, John
Yust-Katz, Shlomit
Yung, Wai-Kwan Alfred
Cohen, Mark L
Aldape, Kenneth D
Rosenfeld, Steven
Verhaak, Roeland G W
Barnholtz-Sloan, Jill S
P30 CA016672/CA/NCI NIH HHS/United States
FP00073233/FP/OFP OASH HHS/United States
P30 CA043703/CA/NCI NIH HHS/United States
U24CA143883/CA/NCI NIH HHS/United States
HHSN261201000057I/CA/NCI NIH HHS/United States
P30 CA015083/CA/NCI NIH HHS/United States
U24 CA143883/CA/NCI NIH HHS/United States
HHSN261201000057C/CA/NCI NIH HHS/United States
P50 CA108961/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
United States
2014/03/13
PLoS One. 2014 Mar 10;9(3):e91216. doi: 10.1371/journal.pone.0091216. eCollection 2014.},
   abstract = {BACKGROUND: Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM) expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas). METHODS: Gene expression array, single nucleotide polymorphism (SNP) array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III) from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson). Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP) was assigned using prediction models by Fine et al. RESULTS: Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs. CONCLUSIONS: GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.},
   keywords = {Brain Neoplasms/*classification/*genetics/pathology
CpG Islands/genetics
DNA Copy Number Variations/genetics
DNA Methylation/genetics
Female
Gene Expression Regulation, Neoplastic
Glioblastoma/*classification/*genetics/pathology
Glioma/*classification/*genetics/pathology
Humans
Isocitrate Dehydrogenase/genetics
Male
Middle Aged
Mutation/genetics
Neoplasm Grading
Survival Analysis},
   ISSN = {1932-6203},
   DOI = {10.1371/journal.pone.0091216},
   year = {2014},
   type = {Journal Article}
}

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