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Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma

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Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma. / DeSisto, John; Lucas Jr, John T; Xu, Ke; Donson, Andrew; Lin, Tong; Sanford, Bridget; Wu, Gang; Tran, Quynh T; Hedges, Dale; Hsu, Chih-Yang; Armstrong, Gregory T; Arnold, Michael; Bhatia, Smita; Flannery, Patrick; Lemma, Rakeb; Hardie, Lakotah; Schüller, Ulrich; Venkataraman, Sujatha; Hoffman, Lindsey M; Dorris, Kathleen; Mulcahy Levy, Jean M; Hankinson, Todd C; Handler, Michael; Liu, Arthur K; Foreman, Nicholas; Vibhakar, Rajeev; Jones, Kenneth; Allen, Sariah; Zhang, Jinghui; Baker, Suzanne J; Merchant, Thomas E; Orr, Brent A; Green, Adam L.

In: NAT COMMUN, Vol. 12, No. 1, 5531, 20.09.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

DeSisto, J, Lucas Jr, JT, Xu, K, Donson, A, Lin, T, Sanford, B, Wu, G, Tran, QT, Hedges, D, Hsu, C-Y, Armstrong, GT, Arnold, M, Bhatia, S, Flannery, P, Lemma, R, Hardie, L, Schüller, U, Venkataraman, S, Hoffman, LM, Dorris, K, Mulcahy Levy, JM, Hankinson, TC, Handler, M, Liu, AK, Foreman, N, Vibhakar, R, Jones, K, Allen, S, Zhang, J, Baker, SJ, Merchant, TE, Orr, BA & Green, AL 2021, 'Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma', NAT COMMUN, vol. 12, no. 1, 5531. https://doi.org/10.1038/s41467-021-25709-x

APA

DeSisto, J., Lucas Jr, J. T., Xu, K., Donson, A., Lin, T., Sanford, B., Wu, G., Tran, Q. T., Hedges, D., Hsu, C-Y., Armstrong, G. T., Arnold, M., Bhatia, S., Flannery, P., Lemma, R., Hardie, L., Schüller, U., Venkataraman, S., Hoffman, L. M., ... Green, A. L. (2021). Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma. NAT COMMUN, 12(1), [5531]. https://doi.org/10.1038/s41467-021-25709-x

Vancouver

DeSisto J, Lucas Jr JT, Xu K, Donson A, Lin T, Sanford B et al. Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma. NAT COMMUN. 2021 Sep 20;12(1). 5531. https://doi.org/10.1038/s41467-021-25709-x

Bibtex

@article{1e4b69e513b64acb9730d037fca1284c,
title = "Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma",
abstract = "Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.",
keywords = "Adolescent, Child, Cohort Studies, Computer Simulation, DNA Copy Number Variations/genetics, DNA Methylation/genetics, Drug Screening Assays, Antitumor, Gene Expression Regulation, Neoplastic, Gene Ontology, Glioma/genetics, Humans, Neoplasm Grading, Radiation, Transcriptome/genetics, Young Adult",
author = "John DeSisto and {Lucas Jr}, {John T} and Ke Xu and Andrew Donson and Tong Lin and Bridget Sanford and Gang Wu and Tran, {Quynh T} and Dale Hedges and Chih-Yang Hsu and Armstrong, {Gregory T} and Michael Arnold and Smita Bhatia and Patrick Flannery and Rakeb Lemma and Lakotah Hardie and Ulrich Sch{\"u}ller and Sujatha Venkataraman and Hoffman, {Lindsey M} and Kathleen Dorris and {Mulcahy Levy}, {Jean M} and Hankinson, {Todd C} and Michael Handler and Liu, {Arthur K} and Nicholas Foreman and Rajeev Vibhakar and Kenneth Jones and Sariah Allen and Jinghui Zhang and Baker, {Suzanne J} and Merchant, {Thomas E} and Orr, {Brent A} and Green, {Adam L}",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = sep,
day = "20",
doi = "10.1038/s41467-021-25709-x",
language = "English",
volume = "12",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma

AU - DeSisto, John

AU - Lucas Jr, John T

AU - Xu, Ke

AU - Donson, Andrew

AU - Lin, Tong

AU - Sanford, Bridget

AU - Wu, Gang

AU - Tran, Quynh T

AU - Hedges, Dale

AU - Hsu, Chih-Yang

AU - Armstrong, Gregory T

AU - Arnold, Michael

AU - Bhatia, Smita

AU - Flannery, Patrick

AU - Lemma, Rakeb

AU - Hardie, Lakotah

AU - Schüller, Ulrich

AU - Venkataraman, Sujatha

AU - Hoffman, Lindsey M

AU - Dorris, Kathleen

AU - Mulcahy Levy, Jean M

AU - Hankinson, Todd C

AU - Handler, Michael

AU - Liu, Arthur K

AU - Foreman, Nicholas

AU - Vibhakar, Rajeev

AU - Jones, Kenneth

AU - Allen, Sariah

AU - Zhang, Jinghui

AU - Baker, Suzanne J

AU - Merchant, Thomas E

AU - Orr, Brent A

AU - Green, Adam L

N1 - © 2021. The Author(s).

PY - 2021/9/20

Y1 - 2021/9/20

N2 - Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.

AB - Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.

KW - Adolescent

KW - Child

KW - Cohort Studies

KW - Computer Simulation

KW - DNA Copy Number Variations/genetics

KW - DNA Methylation/genetics

KW - Drug Screening Assays, Antitumor

KW - Gene Expression Regulation, Neoplastic

KW - Gene Ontology

KW - Glioma/genetics

KW - Humans

KW - Neoplasm Grading

KW - Radiation

KW - Transcriptome/genetics

KW - Young Adult

U2 - 10.1038/s41467-021-25709-x

DO - 10.1038/s41467-021-25709-x

M3 - SCORING: Journal article

C2 - 34545084

VL - 12

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 5531

ER -