Evidence map›Paper›PMID 32767816›Full record

ArticlePigment cell & melanoma research2021

Analysis of CRISPR-Cas9 screens identifies genetic dependencies in melanoma.

Eirini Christodoulou, Mamunur Rashid, Clare Pacini, Alastair Droop, Holly Robertson, Tim van Groningen, Amina F A S Teunisse, Francesco Iorio, Aart G Jochemsen, David J Adams and 1 more

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

Article in Pigment cell & melanoma research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 28 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

11 authors at 2 institutions in 3 countries.

Eirini ChristodoulouDepartment of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0003-4153-7974
Mamunur RashidExperimental Cancer Genetics Group, Wellcome Trust Sanger Institute, Cambridge, UK.
Clare PaciniCancer Dependency Map Analytics, Wellcome Trust Sanger Institute, Cambridge, UK.
Alastair DroopExperimental Cancer Genetics Group, Wellcome Trust Sanger Institute, Cambridge, UK.
Holly RobertsonExperimental Cancer Genetics Group, Wellcome Trust Sanger Institute, Cambridge, UK.
Tim van GroningenDepartment of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Amina F A S TeunisseDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
Francesco IorioCancer Dependency Map Analytics, Wellcome Trust Sanger Institute, Cambridge, UK.ORCID 0000-0001-7063-8913
Aart G JochemsenDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-0570-7967
David J AdamsExperimental Cancer Genetics Group, Wellcome Trust Sanger Institute, Cambridge, UK.ORCID 0000-0001-9490-0306
Remco van DoornDepartment of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-7019-6673
Wellcome Sanger Institute · GBLeiden University Medical Center · NL

Funding

Cancer Research UKMarie Curie 641458Medical Research Council MR/S00386X/1Medical Research Council MR/S00386X/2Medical Research Council MR/V000292/1Wellcome Trust
6 · The paper itself

Abstract

Targeting the MAPK signaling pathway has transformed the treatment of metastatic melanoma. CRISPR-Cas9 genetic screens provide a genome-wide approach to uncover novel genetic dependencies that might serve as therapeutic targets. Here, we analyzed recently reported CRISPR-Cas9 screens comparing data from 28 melanoma cell lines and 313 cell lines of other tumor types in order to identify fitness genes related to melanoma. We found an average of 1,494 fitness genes in each melanoma cell line. We identified 33 genes, inactivation of which specifically reduced the fitness of melanoma. This set of tumor type-specific genes includes established melanoma fitness genes as well as many genes that have not previously been associated with melanoma growth. Several genes encode proteins that can be targeted using available inhibitors. We verified that genetic inactivation of DUSP4 and PPP2R2A reduces the proliferation of melanoma cells. DUSP4 encodes an inhibitor of ERK, suggesting that further activation of MAPK signaling activity through its loss is selectively deleterious to melanoma cells. Collectively, these data present a resource of genetic dependencies in melanoma that may be explored as potential therapeutic targets.

Indexed as

CRISPR-Cas SystemsGenome, HumanCell ProliferationDual-Specificity PhosphatasesGene Knockout TechniquesHumansMelanomaMitogen-Activated Protein Kinase PhosphatasesProtein Phosphatase 2Tumor Cells, CulturedDual-Specificity PhosphatasesDUSP4 protein, humanMitogen-Activated Protein Kinase PhosphatasesPPP2R2A protein, humanProtein Phosphatase 2CRISPR-Cas9 screenDUSP4MAPK signaling pathwaymelanomaPPP2R2A

Identifiers

PMID32767816
PMCPMC7818247
OpenAlexW3047815632

What OpenQuestion holds

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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.