Subgroup and subtype-specific outcomes in adult medulloblastoma.

Adolescent Adult Biomarkers, Tumor / genetics Cerebellar Neoplasms / genetics Cohort Studies Female Humans Male Medulloblastoma / genetics Progression-Free Survival Risk Factors Young Adult
Adult DNA methylation profiling Medulloblastoma Molecular groups Risk stratification

Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
11 2021
Historique:
received: 22 07 2021
accepted: 13 08 2021
revised: 12 08 2021
pubmed: 20 8 2021
medline: 23 2 2022
entrez: 19 8 2021
Statut: ppublish

Résumé

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p < 0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0-86.5), 61.9% (51.6-74.2), 80.0% (95% CI 51.6-100.0), and 44.9% (95% CI 28.6-70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1-7.6; p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3-9.4; p < 0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1-4.8; p = 0.02), and PTCH1 mutations (HR 2.6, 95% CI 1.1-6.2; p = 0.04). The prognostic significance of 3p loss and 10q loss persisted in multivariable regression models. For Group 4 tumours, chromosome 8 loss was strongly associated with improved survival, which was validated in a non-overlapping cohort (combined cohort HR 0.2, 95% CI 0.1-0.7; p = 0.007). Unlike in pediatric medulloblastoma, whole chromosome 11 loss in Group 4 and chromosome 14q loss in SHH was not associated with improved survival, where MYCN, GLI2 and MYC amplification were rare. In sum, we report unique subgroup-specific cytogenetic features of adult medulloblastoma, which are distinct from those in younger patients, and correlate with survival disparities. Our findings suggest that clinical trials that incorporate new strategies tailored to high-risk adult medulloblastoma patients are urgently needed.

Identifiants

DOI: 10.1007/s00401-021-02358-4 PMID: 34409497
pubmed: 34409497
doi: 10.1007/s00401-021-02358-4
pii: 10.1007/s00401-021-02358-4
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

859-871

Subventions

Organisme : NCI NIH HHS
ID : R01NS106155-01
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA235162
Pays : United States
Organisme : NCI NIH HHS
ID : 5R01CA159859-08
Pays : United States
Organisme : NCI NIH HHS
ID : R01NS096236
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS106155
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA159859
Pays : United States

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

Baroni LV, Sampor C, Gonzalez A, Lubieniecki F, Lamas G, Rugilo C et al (2020) Bridging the treatment gap in infant medulloblastoma: molecularly informed outcomes of a globally feasible regimen. Neuro Oncol 22:1873–1881. https://doi.org/10.1093/neuonc/noaa122
doi: 10.1093/neuonc/noaa122 pubmed: 32413139 pmcid: 7746938
Beier D, Proescholdt M, Reinert C, Pietsch T, Jones DTW, Pfister SM et al (2018) Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07). Neuro Oncol 20:400–410. https://doi.org/10.1093/neuonc/nox155
doi: 10.1093/neuonc/nox155 pubmed: 29016837
Brandes AA, Ermani M, Amista P, Basso U, Vastola F, Gardiman M et al (2003) The treatment of adults with medulloblastoma: a prospective study. Int J Radiat Oncol Biol Phys 57:755–761. https://doi.org/10.1016/s0360-3016(03)00643-6
doi: 10.1016/s0360-3016(03)00643-6 pubmed: 14529781
Brandes AA, Franceschi E, Tosoni A, Blatt V, Ermani M (2007) Long-term results of a prospective study on the treatment of medulloblastoma in adults. Cancer 110:2035–2041. https://doi.org/10.1002/cncr.23003
doi: 10.1002/cncr.23003 pubmed: 17823910
Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D et al (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469–474. https://doi.org/10.1038/nature26000
doi: 10.1038/nature26000 pubmed: 29539639 pmcid: 6093218
Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B et al (2017) Intertumoral heterogeneity within medulloblastoma subgroups. Cancer Cell 31(737–754):e736. https://doi.org/10.1016/j.ccell.2017.05.005
doi: 10.1016/j.ccell.2017.05.005
Franceschi E, Hofer S, Brandes AA, Frappaz D, Kortmann RD, Bromberg J et al (2019) EANO-EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma. Lancet Oncol 20:e715–e728. https://doi.org/10.1016/s1470-2045(19)30669-2
doi: 10.1016/s1470-2045(19)30669-2 pubmed: 31797797
Franceschi E, Minichillo S, Mura A, Tosoni A, Mascarin M, Tomasello C et al (2020) Adjuvant chemotherapy in average-risk adult medulloblastoma patients improves survival: a long term study. BMC Cancer 20:755. https://doi.org/10.1186/s12885-020-07237-x
doi: 10.1186/s12885-020-07237-x pubmed: 32787805 pmcid: 7425050
Gaviani P, Simonetti G, Rudà R, Franchino F, Lombardi G, Possanzini M et al (2020) Medulloblastoma of the adult: results from a multicenter retrospective study by AINO (Italian Association of Neuro-Oncology) and SIN (Italian Society of Neurology). Neurol Sci. https://doi.org/10.1007/s10072-020-04556-6
doi: 10.1007/s10072-020-04556-6 pubmed: 32654010
Goschzik T, Schwalbe EC, Hicks D, Smith A, Muehlen AZ, Figarella-Branger D et al (2018) Prognostic effect of whole chromosomal aberration signatures in standard-risk, non-WNT/non-SHH medulloblastoma: a retrospective, molecular analysis of the HIT-SIOP PNET 4 trial. Lancet Oncol 19:1602–1616. https://doi.org/10.1016/s1470-2045(18)30532-1
doi: 10.1016/s1470-2045(18)30532-1 pubmed: 30392813 pmcid: 6262170
Goschzik T, Muehlen AZ, Doerner E, Waha A, Friedrich C, Hau P et al (2021) Medulloblastoma in adults: cytogenetic phenotypes identify prognostic subgroups. J Neuropathol Exp Neurol 80:419–430. https://doi.org/10.1093/jnen/nlab020
doi: 10.1093/jnen/nlab020 pubmed: 33870422
Hovestadt V, Remke M, Kool M, Pietsch T, Northcott PA, Fischer R et al (2013) Robust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumour material using high-density DNA methylation arrays. Acta Neuropathol 125:913–916. https://doi.org/10.1007/s00401-013-1126-5
doi: 10.1007/s00401-013-1126-5 pubmed: 23670100 pmcid: 3661908
Kann BH, Lester-Coll NH, Park HS, Yeboa DN, Kelly JR, Baehring JM et al (2017) Adjuvant chemotherapy and overall survival in adult medulloblastoma. Neuro Oncol 19:259–269. https://doi.org/10.1093/neuonc/now150
doi: 10.1093/neuonc/now150 pubmed: 27540083
Kocakaya S, Beier CP, Beier D (2016) Chemotherapy increases long-term survival in patients with adult medulloblastoma–a literature-based meta-analysis. Neuro Oncol 18:408–416. https://doi.org/10.1093/neuonc/nov185
doi: 10.1093/neuonc/nov185 pubmed: 26359208
Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ, Hovestadt V et al (2014) Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 25:393–405. https://doi.org/10.1016/j.ccr.2014.02.004
doi: 10.1016/j.ccr.2014.02.004 pubmed: 24651015 pmcid: 4493053
Kool M, Korshunov A, Pfister SM (2012) Update on molecular and genetic alterations in adult medulloblastoma. Memo 5:228–232. https://doi.org/10.1007/s12254-012-0037-9
doi: 10.1007/s12254-012-0037-9 pubmed: 23864912 pmcid: 3458193
Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA et al (2012) Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathol 123:473–484. https://doi.org/10.1007/s00401-012-0958-8
doi: 10.1007/s00401-012-0958-8 pubmed: 22358457 pmcid: 3306778
Korshunov A, Okonechnikov K, Stichel D, Ryzhova M, Schrimpf D, Sahm F et al (2021) Integrated molecular analysis of adult Sonic Hedgehog (SHH)-activated medulloblastomas reveals two clinically relevant tumor subsets with VEGFA as potent prognostic indicator. Neuro Oncol. https://doi.org/10.1093/neuonc/noab031
doi: 10.1093/neuonc/noab031 pubmed: 34077956 pmcid: 8168220
Korshunov A, Remke M, Werft W, Benner A, Ryzhova M, Witt H et al (2010) Adult and pediatric medulloblastomas are genetically distinct and require different algorithms for molecular risk stratification. J Clin Oncol 28:3054–3060. https://doi.org/10.1200/jco.2009.25.7121
doi: 10.1200/jco.2009.25.7121 pubmed: 20479417
Lassaletta A, Ramaswamy V (2016) Medulloblastoma in adults: they’re not just big kids. Neuro Oncol 18:895–897. https://doi.org/10.1093/neuonc/now110
doi: 10.1093/neuonc/now110 pubmed: 27271088 pmcid: 4896553
Majd N, Penas-Prado M (2019) Updates on management of adult medulloblastoma. Curr Treat Opt Oncol 20:64. https://doi.org/10.1007/s11864-019-0663-0
doi: 10.1007/s11864-019-0663-0
Nobre L, Zapotocky M, Khan S, Fukuoka K, Fonseca A, McKeown T et al (2020) Pattern of Relapse and treatment response in WNT-activated medulloblastoma. Cell Rep Med. https://doi.org/10.1016/j.xcrm.2020.100038
doi: 10.1016/j.xcrm.2020.100038 pubmed: 32743560 pmcid: 7394286
Nor C, Ramaswamy V (2018) Clinical and pre-clinical utility of genomics in medulloblastoma. Expert Rev Neurother 18:633–647. https://doi.org/10.1080/14737175.2018.1503536
doi: 10.1080/14737175.2018.1503536 pubmed: 30032687
Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T et al (2017) The whole-genome landscape of medulloblastoma subtypes. Nature 547:311–317. https://doi.org/10.1038/nature22973
doi: 10.1038/nature22973 pubmed: 28726821 pmcid: 5905700
Northcott PA, Hielscher T, Dubuc A, Mack S, Shih D, Remke M et al (2011) Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathol 122:231–240. https://doi.org/10.1007/s00401-011-0846-7
doi: 10.1007/s00401-011-0846-7 pubmed: 21681522 pmcid: 4538327
Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C et al (2019) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012–2016. Neuro Oncol 21:v1–v100. https://doi.org/10.1093/neuonc/noz150
doi: 10.1093/neuonc/noz150 pubmed: 31675094 pmcid: 6823730
Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F et al (2016) Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol 131:821–831. https://doi.org/10.1007/s00401-016-1569-6
doi: 10.1007/s00401-016-1569-6 pubmed: 27040285 pmcid: 4867119
Ramaswamy V, Taylor MD (2017) Medulloblastoma: from myth to molecular. J Clin Oncol 35:2355–2363. https://doi.org/10.1200/jco.2017.72.7842
doi: 10.1200/jco.2017.72.7842 pubmed: 28640708
Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A et al (2011) Adult medulloblastoma comprises three major molecular variants. J Clin Oncol 29:2717–2723. https://doi.org/10.1200/jco.2011.34.9373
doi: 10.1200/jco.2011.34.9373 pubmed: 21632505
Remke M, Ramaswamy V, Peacock J, Shih DJ, Koelsche C, Northcott PA et al (2013) TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. Acta Neuropathol 126:917–929. https://doi.org/10.1007/s00401-013-1198-2
doi: 10.1007/s00401-013-1198-2 pubmed: 24174164 pmcid: 3830749
SAS Institute Inc. (2020) Editorial Guidelines https://www.sas.com/en_ca/legal/editorial-guidelines.html . Accessed 02 Apr 2020
Sharma T, Schwalbe EC, Williamson D, Sill M, Hovestadt V, Mynarek M et al (2019) Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes. Acta Neuropathol 138:309–326. https://doi.org/10.1007/s00401-019-02020-0
doi: 10.1007/s00401-019-02020-0 pubmed: 31076851 pmcid: 6660496
Shih DJ, Northcott PA, Remke M, Korshunov A, Ramaswamy V, Kool M et al (2014) Cytogenetic prognostication within medulloblastoma subgroups. J Clin Oncol 32:886–896. https://doi.org/10.1200/JCO.2013.50.9539
doi: 10.1200/JCO.2013.50.9539 pubmed: 24493713 pmcid: 3948094
Skowron P, Farooq H, Cavalli FMG, Morrissy AS, Ly M, Hendrikse LD et al (2021) The transcriptional landscape of Shh medulloblastoma. Nat Commun 12:1749. https://doi.org/10.1038/s41467-021-21883-0
doi: 10.1038/s41467-021-21883-0 pubmed: 33741928 pmcid: 7979819
Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C et al (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–437. https://doi.org/10.1016/j.ccr.2012.08.024
doi: 10.1016/j.ccr.2012.08.024 pubmed: 23079654
Suzuki H, Kumar SA, Shuai S, Diaz-Navarro A, Gutierrez-Fernandez A, De Antonellis P et al (2019) Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma. Nature 574:707–711. https://doi.org/10.1038/s41586-019-1650-0
doi: 10.1038/s41586-019-1650-0 pubmed: 31664194 pmcid: 7141958
Wong GC, Li KK, Wang WW, Liu AP, Huang QJ, Chan AK et al (2020) Clinical and mutational profiles of adult medulloblastoma groups. Acta Neuropathol Commun 8:191. https://doi.org/10.1186/s40478-020-01066-6
doi: 10.1186/s40478-020-01066-6 pubmed: 33172502 pmcid: 7656770
Zhao F, Ohgaki H, Xu L, Giangaspero F, Li C, Li P, Yang Z, Wang B, Wang X, Wang Z, Ai L, Zhang J, Luo L, Liu P (2016) Molecular subgroups of adult medulloblastoma: a long-term single-institution study. Neuro Oncol 18:982–990. https://doi.org/10.1093/neuonc/now050
doi: 10.1093/neuonc/now050 pubmed: 27106407 pmcid: 4896550

Auteurs

Hallie Coltin (H)

Division of Haematology/Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada.
Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.

Lakshmikirupa Sundaresan (L)

Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.

Kyle S Smith (KS)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, MS 325, Room D2058, 262 Danny Thomas Place, Memphis, TN, 38105-3678, USA.

Patryk Skowron (P)

Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.

Luca Massimi (L)

Department of Neurosurgery, Fondazione Policlinico A. Gemelli IRCCS, Catholic University Medical School, Rome, Italy.

Charles G Eberhart (CG)

Department of Neuropathology and Ophthalmic Pathology, Johns Hopkins University, Baltimore, MD, USA.

Karisa C Schreck (KC)

Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.

Nalin Gupta (N)

Departments of Neurological Surgery and Pediatrics, University of California, San Francisco, CA, USA.

William A Weiss (WA)

Departments of Neurology, Neurological Surgery, and Pediatrics, University of California, San Francisco, CA, USA.

Daniela Tirapelli (D)

Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, São Paulo, Brazil.

Carlos Carlotti (C)

Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, São Paulo, Brazil.

Kay K W Li (KKW)

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

Marina Ryzhova (M)

NN Burdenko Neurosurgical Research Centre, Moscow, Russia.

Andrey Golanov (A)

NN Burdenko Neurosurgical Research Centre, Moscow, Russia.

Olga Zheludkova (O)

NN Burdenko Neurosurgical Research Centre, Moscow, Russia.

Oksana Absalyamova (O)

NN Burdenko Neurosurgical Research Centre, Moscow, Russia.

Konstantin Okonechnikov (K)

Hopp Children's Cancer Center Heidelberg (KiTZ) and Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Damian Stichel (D)

Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ) and Department of Neuropathology, University of Heidelberg, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.

Andreas von Deimling (A)

Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ) and Department of Neuropathology, University of Heidelberg, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.

Caterina Giannini (C)

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Scott Raskin (S)

Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC, USA.

Erwin G Van Meir (EG)

Department of Neurosurgery, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.

Jennifer A Chan (JA)

Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.

Daniel Fults (D)

Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA.

Lola B Chambless (LB)

Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, USA.

Seung-Ki Kim (SK)

Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, South Korea.

Alexandre Vasiljevic (A)

Centre de Pathologie et Neuropathologie Est, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.
ONCOFLAM, Neuro-Oncologie Et Neuro-Inflammation Centre de Recherche en Neurosciences de Lyon, Lyon, France.

Cecile Faure-Conter (C)

Department of Pediatrics, Institut d'Hemato-Oncologie Pediatrique, Lyon, France.

Rajeev Vibhakar (R)

Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA.

Shin Jung (S)

Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam, South Korea.

Sarah Leary (S)

Cancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, WA, USA.

Jaume Mora (J)

Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.

Roger E McLendon (RE)

Department of Pathology, Duke University, Durham, NC, USA.

Ian F Pollack (IF)

Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Peter Hauser (P)

2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Wieslawa A Grajkowska (WA)

Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland.

Joshua B Rubin (JB)

Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St Louis Children's Hospital, St Louis, MO, USA.

Marie-Lise C van Veelen (MC)

Department of Neurosurgery, Brain Tumour Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Pim J French (PJ)

Department of Neurology, Brain Tumour Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Johan M Kros (JM)

Department of Pathology, Erasmus University Medical Center, Rotterdam, Netherlands.

Linda M Liau (LM)

Department of Neurosurgery, David Geffen School of Medicine at University of California at Los Angeles, University of California Los Angeles, Los Angeles, CA, 90095, USA.

Stefan M Pfister (SM)

Hopp Children's Cancer Center Heidelberg (KiTZ) and Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany.

Marcel Kool (M)

Hopp Children's Cancer Center Heidelberg (KiTZ) and Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.

Noriyuki Kijima (N)

Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan.

Michael D Taylor (MD)

Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.

Roger J Packer (RJ)

Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC, USA.

Paul A Northcott (PA)

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, MS 325, Room D2058, 262 Danny Thomas Place, Memphis, TN, 38105-3678, USA. paul.northcott@stjude.org.

Andrey Korshunov (A)

Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ) and Department of Neuropathology, University of Heidelberg, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. andrey.korshunov@med.uni-heidelberg.de.

Vijay Ramaswamy (V)

Division of Haematology/Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada. vijay.ramaswamy@sickkids.ca.
Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada. vijay.ramaswamy@sickkids.ca.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. vijay.ramaswamy@sickkids.ca.
ORCID: 0000-0002-6557-895X

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questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Subgroup and subtype-specific outcomes in...
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