Evidence map›Paper›PMID 34398873›Full record

ArticlePLoS genetics2021

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression.

Aziz Aiderus, Justin Y Newberg, Liliana Guzman-Rojas, Ana M Contreras-Sandoval, Amanda L Meshey, Devin J Jones, Felipe Amaya-Manzanares, Roberto Rangel, Jerrold M Ward, Song-Choon Lee and 11 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 42% 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

7 citing papers in PubMed, 7 citations in OpenAlex.

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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

21 authors at 5 institutions in 3 countries.

Aziz AiderusDepartment of Molecular Oncology, Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.ORCID 0000-0002-5920-1929
Justin Y NewbergDepartment of Molecular Oncology, Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.
Liliana Guzman-RojasCancer Research Program, Houston Methodist Research Institute, Houston, Texas, United States of America.
Ana M Contreras-SandovalDepartment of Molecular Oncology, Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.ORCID 0000-0002-4324-9610
Amanda L MesheyDepartment of Molecular Oncology, Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.
Devin J JonesCancer Research Program, Houston Methodist Research Institute, Houston, Texas, United States of America.ORCID 0000-0003-4364-1273
Felipe Amaya-ManzanaresCancer Research Program, Houston Methodist Research Institute, Houston, Texas, United States of America.
Roberto RangelCancer Research Program, Houston Methodist Research Institute, Houston, Texas, United States of America.
Jerrold M WardInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Republic of Singapore.ORCID 0000-0002-6350-8982
Song-Choon LeeInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Republic of Singapore.
Kenneth Hon-Kim BanInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Republic of Singapore.ORCID 0000-0001-7165-8713
Keith RogersInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Republic of Singapore.
Susan M RogersInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Republic of Singapore.
Luxmanan SelvanesanCentre for Translational Cancer Research, Department of Biochemistry, University of Otago, Dunedin, New Zealand.ORCID 0000-0001-8382-0722
Leslie A McNoeCentre for Translational Cancer Research, Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Neal G CopelandCancer Research Program, Houston Methodist Research Institute, Houston, Texas, United States of America.
Nancy A JenkinsCancer Research Program, Houston Methodist Research Institute, Houston, Texas, United States of America.
Kenneth Y TsaiDepartments of Anatomic Pathology & Tumor Biology, Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.ORCID 0000-0001-5325-212X
Michael A BlackCentre for Translational Cancer Research, Department of Biochemistry, University of Otago, Dunedin, New Zealand.ORCID 0000-0003-1174-6054
Karen M MannDepartment of Molecular Oncology, Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.ORCID 0000-0002-7161-4523
Michael B MannDepartment of Molecular Oncology, Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.ORCID 0000-0002-7515-6515
Agency for Science, Technology and Research · SGHouston Methodist · USMoffitt Cancer Center · USUniversity of Otago · NZUniversity of South Florida · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
Tissue, Pathology and BioinformaticsP50CA168536 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI MULE, JAMES J. · 2013 to 2017
$8.5M
NCI NIH HHS P30 CA076292NCI NIH HHS P50 CA168536Wellcome Trust
6 · The paper itself

Abstract

The systematic identification of genetic events driving cellular transformation and tumor progression in the absence of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified both known tumor suppressor genes and novel oncogenic drivers of cuSCC. Functional analysis confirms an oncogenic role for the ZMIZ genes, and tumor suppressive roles for KMT2C, CREBBP and NCOA2, in the initiation or progression of human cuSCC. Taken together, our in vivo screen demonstrates an extremely heterogeneous genetic landscape of cuSCC initiation and progression, which can be harnessed to better understand skin oncogenic etiology and prioritize therapeutic candidates.

Indexed as

Biomarkers, TumorCarcinoma, Squamous CellCell Transformation, NeoplasticCREB-Binding ProteinDisease ProgressionDNA-Binding ProteinsDNA Transposable ElementsGene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansKeratinocytesMutagenesis, InsertionalNuclear Receptor Coactivator 2Sequence Analysis, DNASkin NeoplasmsBiomarkers, TumorCREB-Binding ProteinCREBBP protein, humanDNA-Binding ProteinsDNA Transposable ElementsKMT2C protein, humanNCOA2 protein, humanNuclear Receptor Coactivator 2

Identifiers

PMID34398873
PMCPMC8389471
OpenAlexW3194000178

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.