Structural variants shape driver combinations and outcomes in pediatric high-grade glioma

被引：15

作者：

Dubois, Frank P. B. ^{[1
,2
,3
]}

Shapira, Ofer ^{[1
,2
,3
]}

Greenwald, Noah F. ^{[1
,2
,3
]}

Zack, Travis ^{[1
,2
,3
]}

Wala, Jeremiah ^{[1
,2
,3
]}

Tsai, Jessica W. ^{[3
,4
,5
]}

Crane, Alexander ^{[1
,2
,3
]}

Baguette, Audrey ^{[6
]}

Hadjadj, Djihad ^{[7
]}

Harutyunyan, Ashot S. ^{[7
]}

Kumar, Kiran H. ^{[1
,2
,3
]}

Blattner-Johnson, Mirjam ^{[8
,9
]}

Vogelzang, Jayne ^{[10
]}

Sousa, Cecilia ^{[10
]}

Kang, Kyung Shin ^{[1
,2
,3
]}

Sinai, Claire ^{[10
]}

Wang, Dayle K. ^{[3
,5
]}

Khadka, Prasidda ^{[1
,2
,3
]}

Lewis, Kathleen ^{[3
]}

Nguyen, Lan ^{[3
]}

Malkin, Hayley ^{[10
]}

Ho, Patricia ^{[1
,2
,3
]}

O'Rourke, Ryan ^{[1
,2
,3
]}

Zhang, Shu ^{[1
,2
,3
]}

Gold, Rose ^{[1
,2
,3
]}

Deng, Davy ^{[1
,2
,3
]}

Serrano, Jonathan ^{[11
]}

Snuderl, Matija ^{[11
]}

Jones, Chris ^{[12
]}

Wright, Karen D. ^{[4
,5
]}

Chi, Susan N. ^{[4
,5
]}

Grill, Jacques ^{[13
,14
,15
]}

Kleinman, Claudia L. ^{[7
,16
]}

Goumnerova, Liliana C. ^{[17
,18
,26
]}

Jabado, Nada ^{[7
,19
,20
,21
]}

Jones, David T. W. ^{[8
,9
]}

Kieran, Mark W. ^{[3
,4
,5
,27
]}

Ligon, Keith L. ^{[3
,10
,22
,23
,24
]}

Beroukhim, Rameen ^{[1
,2
,3
,25
]}

Bandopadhayay, Pratiti ^{[3
,4
,5
]}

机构：

[1] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[5] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Oncol, Boston, MA 02115 USA

[6] McGill Univ, Quantitat Life Sci, Boston, MA USA

[7] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[8] Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany

[9] German Canc Res Ctr, German Canc Consortium DKTK, Div Pediat Glioma Res, Heidelberg, Germany

[10] Harvard Med Sch, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA

[11] NYU, Med Ctr, New York, NY 10016 USA

[12] Inst Canc Res, Div Canc Therapeut, 15 Cotswold Rd, Sutton, Surrey, England

[13] Gustave Roussy Inst, Dept Pediat & Adolescent Oncol, Villejuif, France

[14] Gustave Roussy Inst, INSERM Unit 981, Villejuif, France

[15] Univ Paris Saclay, Villejuif, France

[16] Jewish Gen Hosp, Lady Davis Res Inst, Montreal, PQ, Canada

[17] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA

[18] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA

[19] McGill Univ, Dept Med, Div Expt Med, Montreal, PQ, Canada

[20] McGill Univ, Dept Pediat, Montreal, PQ, Canada

[21] McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada

[22] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[23] Boston Childrens Hosp, Boston, MA 02115 USA

[24] Dana Farber Canc Inst, Ctr Patient Derived Models, Boston, MA 02115 USA

[25] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA

[26] Tromboprotea, San Francisco, CA USA

[27] Day One Biopharmaceut, San Francisco, CA USA

来源：

NATURE CANCER | 2022年 / 3卷 / 08期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

INTRINSIC PONTINE GLIOMAS; SURGICAL BIOPSY; HISTONE H3.3; MUTATIONS; GENOME; CANCER; DNA; GENES; SUBGROUPS; CHROMATIN;

D O I：

10.1038/s43018-022-00403-z

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53(WT)) but showed alterations in TP53 pathway members PPM1D and MDM4. Complex signatures were associated with direct aberrations in TP53, CDKN2A and RB1 early in tumor evolution and with later-occurring extrachromosomal amplicons. All pHGGs exhibited at least one simple-SV signature, but complex-SV signatures were primarily restricted to subsets of H3.3(K27M) DMGs and hemispheric pHGGs. Importantly, DMGs with complex-SV signatures were associated with shorter overall survival independent of histone mutation and TP53 status. These data provide insight into the impact of SVs on gliomagenesis and the mechanisms that shape them. Dubois and colleagues assemble a large cohort of human pediatric high-grade glioma samples, identifying patterns of simple and complex structural variants and characterizing their role in tumor development and evolution.

引用

页码：994 / +

页数：39

共 80 条

[31] APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication
Hoopes, James I.
Cortez, Luis M.
Mertz, Tony M.
Malc, Ewa P.
Mieczkowski, Piotr A.
Roberts, Steven A.
[J]. CELL REPORTS, 2016, 14 (06): : 1273 - 1282
[32] Insertions and Deletions Target Lineage-Defining Genes in Human Cancers
Imielinski, Marcin
Guo, Guangwu
Meyerson, Matthew
[J]. CELL, 2017, 168 (03) : 460 - +
[33] Adjusting batch effects in microarray expression data using empirical Bayes methods
Johnson, W. Evan
Li, Cheng
Rabinovic, Ariel
[J]. BIOSTATISTICS, 2007, 8 (01) : 118 - 127
[34] Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers
Kim, Hoon
Nguyen, Nam-Phuong
Turner, Kristen
Wu, Sihan
Gujar, Amit D.
Luebeck, Jens
Liu, Jihe
Deshpande, Viraj
Rajkumar, Utkrisht
Namburi, Sandeep
Amin, Samirkumar B.
Yi, Eunhee
Menghi, Francesca
Schulte, Johannes H.
Henssen, Anton G.
Chang, Howard Y.
Beck, Christine R.
Mischel, Paul S.
Bafna, Vineet
Verhaak, Roel G. W.
[J]. NATURE GENETICS, 2020, 52 (09) : 891 - +
[35] Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors
Kim, Jaegil
Mouw, Kent W.
Polak, Paz
Braunstein, Lior Z.
Kamburov, Atanas
Tiao, Grace
Kwiatkowski, David J.
Rosenberg, Jonathan E.
Van Allen, Eliezer M.
D'Andrea, Alan D.
Getz, Gad
[J]. NATURE GENETICS, 2016, 48 (06) : 600 - +
[36] Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma
Koche, Richard P.
Rodriguez-Fos, Elias
Helmsauer, Konstantin
Burkert, Martin
MacArthur, Ian C.
Maag, Jesper
Chamorro, Rocio
Munoz-Perez, Natalia
Puiggros, Montserrat
Dorado Garcia, Heathcliff
Bei, Yi
Roeefzaad, Claudia
Bardinet, Victor
Szymansky, Annabell
Winkler, Annika
Thole, Theresa
Timme, Natalie
Kasack, Katharina
Fuchs, Steffen
Klironomos, Filippos
Thiessen, Nina
Blanc, Eric
Schmelz, Karin
Kuenkele, Annette
Hundsdoerfer, Patrick
Rosswog, Carolina
Theissen, Jessica
Beule, Dieter
Deubzer, Hedwig
Sauer, Sascha
Toedling, Joern
Fischer, Matthias
Hertwig, Falk
Schwarz, Roland F.
Eggert, Angelika
Torrents, David
Schulte, Johannes H.
Henssen, Anton G.
[J]. NATURE GENETICS, 2020, 52 (01) : 29 - +
[37] Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas
Krug, Brian
De Jay, Nicolas
Harutyunyan, Ashot S.
Deshmukh, Shriya
Marchione, Dylan M.
Guilhamon, Paul
Bertrand, Kelsey C.
Mikael, Leonie G.
McConechy, Melissa K.
Chen, Carol C. L.
Khazaei, Sima
Koncar, Robert F.
Agnihotri, Sameer
Faury, Damien
Ellezam, Benjamin
Weil, Alexander G.
Ursini-Siegel, Josie
De Carvalho, Daniel D.
Dirks, Peter B.
Lewis, Peter W.
Salomoni, Paolo
Lupien, Mathieu
Arrowsmith, Cheryl
Lasko, Paul F.
Garcia, Benjamin A.
Kleinman, Claudia L.
Jabado, Nada
Mack, Stephen C.
[J]. CANCER CELL, 2019, 35 (05) : 782 - +
[38] Mutational heterogeneity in cancer and the search for new cancer-associated genes
Lawrence, Michael S.
Stojanov, Petar
Polak, Paz
Kryukov, Gregory V.
Cibulskis, Kristian
Sivachenko, Andrey
Carter, Scott L.
Stewart, Chip
Mermel, Craig H.
Roberts, Steven A.
Kiezun, Adam
Hammerman, Peter S.
McKenna, Aaron
Drier, Yotam
Zou, Lihua
Ramos, Alex H.
Pugh, Trevor J.
Stransky, Nicolas
Helman, Elena
Kim, Jaegil
Sougnez, Carrie
Ambrogio, Lauren
Nickerson, Elizabeth
Shefler, Erica
Cortes, Maria L.
Auclair, Daniel
Saksena, Gordon
Voet, Douglas
Noble, Michael
DiCara, Daniel
Lin, Pei
Lichtenstein, Lee
Heiman, David I.
Fennell, Timothy
Imielinski, Marcin
Hernandez, Bryan
Hodis, Eran
Baca, Sylvan
Dulak, Austin M.
Lohr, Jens
Landau, Dan-Avi
Wu, Catherine J.
Melendez-Zajgla, Jorge
Hidalgo-Miranda, Alfredo
Koren, Amnon
McCarroll, Steven A.
Mora, Jaume
Lee, Ryan S.
Crompton, Brian
Onofrio, Robert
[J]. NATURE, 2013, 499 (7457) : 214 - 218
[39] The sva package for removing batch effects and other unwanted variation in high-throughput experiments
Leek, Jeffrey T.
Johnson, W. Evan
Parker, Hilary S.
Jaffe, Andrew E.
Storey, John D.
[J]. BIOINFORMATICS, 2012, 28 (06) : 882 - 883
[40] REJOINING OF X-RAY INDUCED BREAKS IN DNA OF LEUKAEMIA CELLS
LETT, JT
CALDWELL, I
DEAN, CJ
ALEXANDER, P
[J]. NATURE, 1967, 214 (5090) : 790 - +

← 1 2 3 4 5 6 7 8 →