Characterizing temporal genomic heterogeneity in pediatric high-grade gliomas

Acta Neuropathologica Communications
Ralph SalloumNada Jabado

Abstract

Pediatric high-grade gliomas (pHGGs) are aggressive neoplasms representing approximately 20% of brain tumors in children. Current therapies offer limited disease control, and patients have a poor prognosis. Empiric use of targeted therapy, especially at progression, is increasingly practiced despite a paucity of data regarding temporal and therapy-driven genomic evolution in pHGGs. To study the genetic landscape of pHGGs at recurrence, we performed whole exome and methylation analyses on matched primary and recurrent pHGGs from 16 patients. Tumor mutational profiles identified three distinct subgroups. Group 1 (n = 7) harbored known hotspot mutations in Histone 3 (H3) (K27M or G34V) or IDH1 (H3/IDH1 mutants) and co-occurring TP53 or ACVR1 mutations in tumor pairs across the disease course. Group 2 (n = 7), H3/IDH1 wildtype tumor pairs, harbored novel mutations in chromatin modifiers (ZMYND11, EP300 n = 2), all associated with TP53 alterations, or had BRAF V600E mutations (n = 2) conserved across tumor pairs. Group 3 included 2 tumors with NF1 germline mutations. Pairs from primary and relapsed pHGG samples clustered within the same DNA methylation subgroup. ATRX mutations were clonal and retained in H3G34V and H3/IDH1 wildtype ...Continue Reading

References

Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
Mar 29, 2007·Brain Pathology·Anika EckertJohannes Gebert
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Nov 6, 2008·Acta Neuropathologica·Jörg BalssAndreas von Deimling
Feb 21, 2009·The New England Journal of Medicine·Hai YanDarell D Bigner
May 19, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Barbara S PaughSuzanne J Baker
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Mar 11, 2011·Nature·Laura PasqualucciRiccardo Dalla-Favera
Jan 31, 2012·Nature Genetics·Gang WuUNKNOWN St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project
Mar 19, 2013·Cell·Jan O Korbel, Peter J Campbell
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Aug 13, 2013·Nature Structural & Molecular Biology·Manuela DelvecchioDaniel Panne
Oct 15, 2013·Cell·Cameron W BrennanUNKNOWN TCGA Research Network
Oct 22, 2013·The Lancet Oncology·Vijay RamaswamyMichael D Taylor
Dec 4, 2013·Genes & Development·Cheng-Zhong ZhangDavid Pellman
Apr 8, 2014·Nature Genetics·Adam M FontebassoMark W Kieran
Apr 8, 2014·Nature Genetics·Kathryn R TaylorJacques Grill
Aug 1, 2014·Acta Neuropathologica·Adam M FontebassoNada Jabado
Nov 29, 2014·Current Protocols in Bioinformatics·Geraldine A Van der AuweraMark A DePristo
Feb 19, 2015·Acta Neuropathologica·Xin WangMichael D Taylor
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Jun 2, 2015·Nature Medicine·Giulia SiravegnaAlberto Bardelli
Jun 11, 2015·The New England Journal of Medicine·Jeanette E Eckel-PassowRobert B Jenkins
Jan 14, 2016·Nature·A Sorana MorrissyMichael D Taylor
Feb 9, 2016·Nature Medicine·Himisha BeltranFrancesca Demichelis
Mar 24, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric BouffetUri Tabori
Apr 7, 2016·Nature Communications·Hamid NikbakhtJavad Nazarian
May 14, 2016·Expert Opinion on Investigational Drugs·Verena StaedtkeJohn Laterra
Jun 9, 2016·Nature Genetics·Jiguang WangRaul Rabadan

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Citations

Oct 4, 2018·Medical Sciences : Open Access Journal·Ugo TestaElvira Pelosi
Oct 2, 2020·Pediatric Blood & Cancer·Laura C GebenAdam J Esbenshade
Dec 28, 2018·NPJ Precision Oncology·Erin R BonnerJavad Nazarian
Jul 10, 2020·Neuro-oncology Advances·Amanda De Andrade Costa, David H Gutmann
Feb 8, 2020·Current Oncology Reports·Kyle WierzbickiCarl Koschmann
Oct 3, 2020·International Journal of Molecular Sciences·Maya S Graham, Ingo K Mellinghoff
Jul 6, 2018·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Doreen N PalsgroveFausto J Rodriguez
Sep 19, 2020·International Journal of Molecular Sciences·Giulia PericoliMaria Vinci
Mar 17, 2019·Cancer Research·Mary HoffmanMarco Gallo
Jan 12, 2021·The American Journal of Surgical Pathology·Francesca GiannoFrancesca R Buttarelli
Nov 7, 2020·Acta Neuropathologica Communications·Margot A LazowChristine Fuller
Feb 10, 2021·Cancer Discovery·James G Nicholson, Howard A Fine
Apr 4, 2021·Cancers·Nathalie OlympiosMaxime Fontanilles

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Methods Mentioned

BETA
exome sequencing
PCR
chips
acetylation

Software Mentioned

ExomeAI
CNAXX
GATK HaplotypeCaller
SAMtools
FishingCNV
Genome Analysis Toolkit ( GATK )
R
FreeBayes
FASTX Toolkit
ANNOVAR

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