Evidence map›Paper›PMID 28067913›Full record

ArticleNature genetics2017

Impaired H3K36 methylation defines a subset of head and neck squamous cell carcinomas.

Simon Papillon-Cavanagh, Chao Lu, Tenzin Gayden, Leonie G Mikael, Denise Bechet, Christina Karamboulas, Laurie Ailles, Jason Karamchandani, Dylan M Marchione, Benjamin A Garcia and 13 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
173citing papers in PubMed, 2 pooled it
11.4field-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

173 citing papers in PubMed, 2 syntheses or guidelines pooled it, 242 citations in OpenAlex.

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113 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 10 institutions in 2 countries.

Simon Papillon-CavanaghDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-0372-2266
Chao LuLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.ORCID http://orcid.org/0000-0003-0982-8122
Tenzin GaydenDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Leonie G MikaelDepartment of Pediatrics, McGill University and McGill University Heath Centre Research Institute, Montreal, Quebec, Canada.
Denise BechetDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Christina KaramboulasPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
Laurie AillesPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
Jason KaramchandaniDepartment of Pathology, Montreal Neurological Hospital, McGill University, Montreal, Quebec, Canada.
Dylan M MarchioneEpigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Benjamin A GarciaEpigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ilan WeinrebDepartment of Pathology, University Health Network, Toronto, Ontario, Canada.
David GoldsteinDepartment of Otolaryngology and Department of Surgical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Peter W LewisWisconsin Institute for Discovery and Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Octavia Maria DancuDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-2596-7843
Sandeep DhaliwalDepartment of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada.
William StechoDepartment of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada.
Christopher J HowlettDepartment of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada.
Joe S MymrykDepartment of Microbiology and Immunology, Oncology and Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada.
John W BarrettDepartment of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada.
Anthony C NicholsDepartment of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada.ORCID http://orcid.org/0000-0002-0760-980X
C David AllisLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.
Jacek MajewskiDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-3572-9558
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Western University · CAMcGill University · CAMcGill University Health Centre · CAPrincess Margaret Cancer Centre · CARockefeller University · USUniversity Health Network · CAMontreal Neurological Institute and Hospital · CATranslational Therapeutics (United States) · USUniversity of Pennsylvania · USUniversity of Wisconsin–Madison · US

Funding

Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6M
STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008275 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI WAND, A. JOSHUA · 1988 to 2018
$6.0M
NSD1 Inactivation in Head and Neck CancerK99CA212257 · NCI · ROCKEFELLER UNIVERSITY · PI LU, CHAO · 2016 to 2017
$276k
NCI NIH HHS K99 CA212257NCI NIH HHS P01 CA196539NIGMS NIH HHS T32 GM008275
6 · The paper itself

Abstract

Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs) are deadly and common cancers. Recent genomic studies implicate multiple genetic pathways, including cell signaling, cell cycle and immune evasion, in their development. Here we analyze public data sets and uncover a previously unappreciated role of epigenome deregulation in the genesis of 13% of HPV-negative HNSCCs. Specifically, we identify novel recurrent mutations encoding p.Lys36Met (K36M) alterations in multiple H3 histone genes. histones. We further validate the presence of these alterations in multiple independent HNSCC data sets and show that, along with previously described NSD1 mutations, they correspond to a specific DNA methylation cluster. The K36M substitution and NSD1 defects converge on altering methylation of histone H3 at K36 (H3K36), subsequently blocking cellular differentiation and promoting oncogenesis. Our data further indicate limited redundancy for NSD family members in HPV-negative HNSCCs and suggest a potential role for impaired H3K36 methylation in their development. Further investigation of drugs targeting chromatin regulators is warranted in HPV-negative HNSCCs driven by aberrant H3K36 methylation.

Indexed as

CarcinogenesisCarcinoma, Squamous CellCell DifferentiationDNA MethylationEpigenesis, GeneticHead and Neck NeoplasmsHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHistonesHumansIntracellular Signaling Peptides and ProteinsMutationNuclear ProteinsPapillomaviridaePapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHistonesIntracellular Signaling Peptides and ProteinsNSD1 protein, humanNuclear Proteins

Identifiers

PMID28067913
PMCPMC5549104
OpenAlexW2571023129

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.