Evidence map›Paper›PMID 29753700›Full record

ArticleThe Lancet. Oncology2018

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

Sebastian M Waszak, Paul A Northcott, Ivo Buchhalter, Giles W Robinson, Christian Sutter, Susanne Groebner, Kerstin B Grund, Laurence Brugières, David T W Jones, Kristian W Pajtler and 77 more

Open access · bronzeAbstract readMulticenter StudyValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
228citing papers in PubMed, 2 pooled it
26.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

228 citing papers in PubMed, 2 syntheses or guidelines pooled it, 389 citations in OpenAlex.

  1. Guideline
  2. SEOM clinical guideline for management of adult medulloblastoma (2020).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
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168 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

87 authors at 20 institutions in 16 countries.

Sebastian M WaszakEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Paul A NorthcottDivision of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
Ivo BuchhalterDivision of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany; Division of Applied Bioinformatics, German Cancer Research Center, Heidelberg, Germany.
Giles W RobinsonDepartment of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
Christian SutterInstitute of Human Genetics, Heidelberg University, Heidelberg, Germany.
Susanne GroebnerDivision of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Kerstin B GrundInstitute of Human Genetics, Heidelberg University, Heidelberg, Germany.
Laurence BrugièresDepartment of Children and Adolescents Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
David T W JonesDivision of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany.
Kristian W PajtlerDepartment of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany.
A Sorana MorrissyDepartment of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Marcel KoolDivision of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany.
Dominik SturmDepartment of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany.
Lukas ChavezDivision of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Aurelie ErnstDivision of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
Sebastian BrabetzDepartment of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany.
Michael HainDivision of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
Thomas ZichnerEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Maia Segura-WangEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Joachim WeischenfeldtBiotech Research and Innovation Centre, Copenhagen, Denmark; Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Tobias RauschEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Balca R MardinEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Xin ZhouDepartment of Computational Biology, St Jude Children's Research Hospital, Memphis, TN, USA.
Cristina BaciuUniversity Health Network-Toronto General Hospital, Toronto, ON, Canada.
Christian LawerenzData Management Facility, German Cancer Research Center, Heidelberg, Germany.
Jennifer A ChanDepartment of Pathology and Laboratory Medicine, Department of Oncology, and Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
Pascale VarletDepartment of Neuropathology, Sainte-Anne Hospital, Paris, France.
Lea Guerrini-RousseauDepartment of Children and Adolescents Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
Daniel W FultsDepartment of Neurosurgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
Wiesława GrajkowskaDepartment of Pathology, Children's Memorial Health Institute, Warsaw, Poland.
Peter Hauser2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Nada JabadoDepartment of Pediatrics, McGill University, Montreal, QC, Canada.
Young-Shin RaDepartment of Neurosurgery, Asan Medical Center, Seoul, South Korea.
Karel ZitterbartDepartment of Paediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Suyash S ShringarpureDepartments of Genetics and Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Francisco M De La VegaDepartments of Genetics and Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Carlos D BustamanteDepartments of Genetics and Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Ho-Keung NgDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
Arie PerryDivision of Neuropathology, Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Tobey J MacDonaldDepartment of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, USA.
Pablo Hernáiz DrieverKlinik für Pädiatrie mS Onkologie und Hämatologie, Charité, Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Anne E BendelDepartment of Pediatric Hematology and Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN, USA.
Daniel C BowersDivision of Pediatric Hematology-Oncology, University of Texas Southwestern Medical School, Dallas, TX, USA.
Geoffrey McCowageDepartment of Paediatric Oncology, The Children's Hospital at Westmead, Sydney, NSW, Australia.
Murali M ChintagumpalaDepartment of Pediatric Hematology and Oncology, Texas Children's Hospital, Houston, TX, USA.
Richard CohnDepartment of Paediatric Oncology, Sydney Children's Hospital, Sydney, NSW, Australia.
Timothy HassallDepartment of Paediatric Oncology, Lady Cilento Children's Hospital, South Brisbane, QLD, Australia.
Gudrun FleischhackPediatric Oncology and Hematology, Pediatrics III, University Hospital of Essen, Essen, Germany.
Tone EggenCancer Registry of Norway, Oslo, Norway.
Finn WesenbergDepartment of Pediatric Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Cancer Registry of Norway, Oslo, Norway.
Maria FeychtingInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Birgitta LanneringDepartment of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, Gothenburg, Sweden.
Joachim SchüzSection of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.
Christoffer JohansenOncology Clinic, Finsen Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Unit of Survivorship, Copenhagen, Denmark.
Tina V AndersenDanish Cancer Society Research Center, Copenhagen, Denmark.
Martin RöösliDepartment of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.
Claudia E KuehniSwiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Michael GrotzerDepartment of Pediatric Oncology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Kristina KjaerheimCancer Registry of Norway, Oslo, Norway.
Camelia M MonoranuComprehensive Cancer Center Mainfranken, Würzburg, Germany; Department of Neuropathology, Institute of Pathology, University of Würzburg, Würzburg, Germany.
Tenley C ArcherBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Elizabeth DukeDepartment of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Scott L PomeroyBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Redmond ShelaghSwiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Stephan FrankInstitute of Neuropathology, University Hospital Basel, Basel, Switzerland.
David SumerauerDepartment of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic.
Wolfram ScheurlenCnopf'sche Kinderklinik, Nuremberg, Germany.
Marina V RyzhovaDepartment of Neuropathology, Burdenko Neurosurgical Institute, Moscow, Russia.
Till MildeDepartment of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany.
Christian P KratzPediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
David SamuelValley Children's Hospital, Madera, CA, USA.
Jinghui ZhangDepartment of Computational Biology, St Jude Children's Research Hospital, Memphis, TN, USA.
David A SolomonDivision of Neuropathology, Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Marco MarraMichael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
Roland EilsDivision of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany.
Claus R BartramInstitute of Human Genetics, Heidelberg University, Heidelberg, Germany.
Katja von HoffDepartment of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Klinik für Pädiatrie mS Onkologie und Hämatologie, Charité, Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Stefan RutkowskiDepartment of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Vijay RamaswamyDivision of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
Richard J GilbertsonDepartment of Oncology and Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Andrey KorshunovDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany.
Michael D TaylorDivision of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada.
Peter LichterDivision of Molecular Genetics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
David MalkinDivision of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
Amar GajjarDepartment of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
Jan O KorbelEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Stefan M PfisterDepartment of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg, Germany. Electronic address: s.pfister@kitz-heidelberg.de.
Heidelberg University · DEEuropean Molecular Biology Laboratory · DEGerman Cancer Research Center · DESt. Jude Children's Research Hospital · USStanford University · USBroad Institute · USCancer Registry of Norway · NOHopp Children's Cancer Center Heidelberg · DEInstitut Gustave Roussy · FRUniversity of Calgary · CAUniversity of California, San Francisco · USUniversity of Toronto · CAAsan Medical Center · KRBurdenko Neurosurgery Institute · RUCanada's Michael Smith Genome Sciences Centre · CACentre Hospitalier Sainte-Anne · FRCentre International de Recherche sur le Cancer · FRCharité - Universitätsmedizin Berlin · DECharles University · CZChildren's Hospital at Westmead · AU

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
The DNA Damage Response and Tumorigenesis in the BrainP01CA096832 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BAKER, SUZANNE J. · 2003 to 2025
$38.0M
TRAINING IN SLEEP, CIRCADIAN &RESPIRATORY NEUROBIOLOGYT32HL007901 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Charles A Czeisler · 1998 to 2026
$18.5M
Mouse models to discover new drivers of medulloblastomaR01CA159859 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael D. Taylor, WILLIAM A WEISS · 2011 to 2026
$10.4M
GENOMIC ANALYSIS OF MEDULLOBLASTOMASR01CA109467 · NCI · CHILDREN'S HOSPITAL BOSTON · PI MESIROV, JILL P., POMEROY, SCOTT LOREN · 2004 to 2015
$7.3M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI CHEN, CHINFEI · 2016 to 2020
$5.2M
Embryonal Brain Tumor NetworksU01CA184898 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI FRAENKEL, ERNEST, MESIROV, JILL P. · 2014 to 2019
$3.6M
Medulloblastoma and MetastasesR01CA148699 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TAYLOR, MICHAEL D., WEISS, WILLIAM A · 2010 to 2014
$2.4M
Cancer Research UK 22492Cancer Research UK A17197European Research Council 336045NCI NIH HHS P01 CA096832NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA109467NCI NIH HHS R01 CA148699NCI NIH HHS R01 CA159859NCI NIH HHS U01 CA184898NHLBI NIH HHS T32 HL007901NICHD NIH HHS U54 HD090255World Health Organization 001
6 · The paper itself

Abstract

backgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.

methodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB

findingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MB

interpretationGenetic counselling and testing should be used as a standard-of-care procedure in patients with MB

fundingGerman Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.

Indexed as

DNA MethylationGerm-Line MutationModels, GeneticAdolescentAdultBiomarkers, TumorCerebellar NeoplasmsChildChild, PreschoolDNA Mutational AnalysisExome SequencingFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGenetic TestingHeredityBiomarkers, Tumor

Identifiers

PMID29753700
PMCPMC5984248
OpenAlexW2799574682

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.