ArticleCancer discovery2021
Mutations in the RAS/MAPK Pathway Drive Replication Repair-Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition.
Open access · bronzeAbstract readMulticenter Study
In one paragraph
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
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.
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.
Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Cellular and Immunotherapy for Pediatric Brain Tumors: A Primer.Current oncology (Toronto, Ont.) · 2026Review
- RAS/MAPK inhibition in pediatric gliomas.Neuro-oncology advances · 2026Review
- Immune-Genomic Evolution in AML Spontaneous Remission: A 66-Patient Pooled Analysis and Longitudinal Clonal Tracking.Cancers · 2026Article
- Sustained response to trametinib in an adult patient with neurofibromatosis type 1 and high-grade glioma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Article
- The Role of the Gut Microbiota in Modulating Signaling Pathways and Oxidative Stress in Glioma Therapies.Cancers · 2025Review
- Immune checkpoint inhibitors for glioblastoma: emerging science, clinical advances, and future directions.Journal of neuro-oncology · 2025Review
- Report of the sixth meeting of the European Consortium 'Care for CMMRD' (CFamilial cancer · 2024Article
- Precision immuno-oncology approach for four malignant tumors in siblings with constitutional mismatch repair deficiency syndrome.NPJ precision oncology · 2024Article
- Zebrafish-A Suitable Model for Rapid Translation of Effective Therapies for Pediatric Cancers.Cancers · 2024Review
- Review
- Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti-PD-1 Monotherapy: A Report from the International RRD Consortium.Cancer discovery · 2024Article
- Neurofibromatosis type 1 mosaicism in patients with constitutional mismatch repair deficiency.Journal of medical genetics · 2024Article
- "De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade.Acta neuropathologica · 2023Article
- Efficacy of Nivolumab in Pediatric Cancers with High Mutation Burden and Mismatch Repair Deficiency.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- MAPK signaling pathway-based glioma subtypes, machine-learning risk model, and key hub proteins identification.Scientific reports · 2023Article
- Integrated analysis of racial disparities in genomic architecture identifies a trans-ancestry prognostic subtype in bladder cancer.Molecular oncology · 2023Article
- Integrated molecular and clinical analysis of BRAF-mutant glioma in adults.NPJ precision oncology · 2023Article
- Hereditary cancer syndromes.World journal of clinical oncology · 2023Review
- Recurrent posterior fossa group A (PFA) ependymoma in a young child with constitutional mismatch repair deficiency (CMMRD).Neuropathology and applied neurobiology · 2023Article
- A New View of Activating Mutations in Cancer.Cancer research · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 10 institutions in 4 countries.
Brittany B Campbell *Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Melissa A Galati *Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Simone C StonePrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Alexandra N RiemenschneiderThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Melissa EdwardsProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Sumedha SudhamanProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Robert SiddawayThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID 0000-0003-2013-9467
Martin KomosaProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Nuno M NunesProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID 0000-0002-3879-9757
Liana NobreProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
A Sorana MorrissyCharbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.ORCID 0000-0001-8526-562X
Matthew ZatzmanProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Michal ZapotockyThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Lazar JoksimovicProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Sangeetha N KalimuthuDepartment of Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Ontario, Canada.
David SamuelDepartment of Hematology-Oncology, Valley Children's Hospital, Madera, California.ORCID 0000-0001-6850-4932
Gary MasonDepartment of Pediatric Hematology-Oncology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
Eric BouffetDivision of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-6832-6539
Daniel A MorgensternDivision of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-4859-1108
Melyssa AronsonZane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
Carol DurnoZane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
David MalkinProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
John M MarisDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-8088-7929
Michael D TaylorThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Adam ShlienProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Trevor J PughPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0002-8073-5888
Pamela S OhashiPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0003-2915-9317
Cynthia E HawkinsThe Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Uri TaboriProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. uri.tabori@sickkids.ca.
Hospital for Sick Children · CAUniversity of Toronto · CAMount Sinai Hospital · CAAlberta Cancer Foundation · CAChildren's Hospital Central California · USChildren's Hospital of Philadelphia · USChildren's Hospital of Pittsburgh · USOntario Institute for Cancer Research · CAPrincess Margaret Cancer Centre · CAUniversity Health Network · CA
Funding
Discovering mechanisms of neuroblastoma tumorigenesis to improve patient outcomesR35CA220500 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI JOHN M MARIS · 2017 to 2026
$8.7MCanadian Institutes for Health ResearchNCI NIH HHS R35 CA220500
Abstract
The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors that harbor many somatic mutations may obscure the interpretation of such targetable genomic events. We find that replication repair-deficient (RRD) cancers, which are universally hypermutant and affect children born with RRD cancer predisposition, are enriched for
Indexed as
Genetic Predisposition to DiseaseAdultAnimalsAntineoplastic AgentsBrain NeoplasmsCell Line, TumorChildColorectal NeoplasmsFemaleGliomaGlobal HealthHumansMaleMiceMice, Inbred NODMitogen-Activated Protein Kinase KinasesAntineoplastic AgentsMitogen-Activated Protein Kinase KinasesProtein Kinase Inhibitors
Identifiers
What Socratic holds
Textmetadata
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Read underepoch 390
Registered trials
None linked
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 Socratic graph.