Evidence map›Paper›PMID 37024492›Full record

ArticleNature communications2023

Mapping the landscape of genetic dependencies in chordoma.

Tanaz Sharifnia, Mathias J Wawer, Amy Goodale, Yenarae Lee, Mariya Kazachkova, Joshua M Dempster, Sandrine Muller, Joan Levy, Daniel M Freed, Josh Sommer and 6 more

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

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. A framework for target discovery in rare cancers.bioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Chordoma: Genetics and Contemporary Management.International journal of molecular sciences · 2024
    Review
  12. Article
  13. Article
  14. Review
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

16 authors at 2 institutions in 2 countries.

Tanaz Sharifnia *Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. tanaz@broadinstitute.org.ORCID 0000-0001-7274-164X
Mathias J Wawer *Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID 0000-0001-6664-0930
Amy GoodaleBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Yenarae LeeBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Mariya KazachkovaBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Joshua M DempsterBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID 0000-0002-3634-9576
Sandrine MullerBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Joan LevyChordoma Foundation, Durham, NC, 27702, USA.
Daniel M FreedChordoma Foundation, Durham, NC, 27702, USA.
Josh SommerChordoma Foundation, Durham, NC, 27702, USA.
Jérémie KalfonBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Francisca VazquezBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
William C HahnBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID 0000-0003-2840-9791
David E RootBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID 0000-0001-5122-861X
Paul A ClemonsBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.ORCID 0000-0002-1800-5112
Stuart L SchreiberBroad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. stuart_schreiber@harvard.edu.ORCID 0000-0003-1922-7558
Broad Institute · USChordoma Foundation · US

Funding

The Dana-Farber Cancer Institute Cancer Target Discovery and Development CenterU01CA176058 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2013 to 2021
$7.8M
Targeting vulnerabilities of therapy-resistant cancer cell states with small moleculesU01CA217848 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2017 to 2021
$5.8M
Cancer dependencies associated with genomic alterations and targeted by small molU01CA176152 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2013 to 2016
$4.4M
Translating novel cancer targets and mechanisms from the CTD^2 Network using molecular gluesU01CA272612 · NCI · BROAD INSTITUTE, INC. · PI CLEMONS, PAUL ANDREW, SCHREIBER, STUART L · 2022 to 2023
$1.9M
NCI NIH HHS U01 CA176058NCI NIH HHS U01 CA176152NCI NIH HHS U01 CA217848NCI NIH HHS U01 CA272612
6 · The paper itself

Abstract

Identifying the spectrum of genes required for cancer cell survival can reveal essential cancer circuitry and therapeutic targets, but such a map remains incomplete for many cancer types. We apply genome-scale CRISPR-Cas9 loss-of-function screens to map the landscape of selectively essential genes in chordoma, a bone cancer with few validated targets. This approach confirms a known chordoma dependency, TBXT (T; brachyury), and identifies a range of additional dependencies, including PTPN11, ADAR, PRKRA, LUC7L2, SRRM2, SLC2A1, SLC7A5, FANCM, and THAP1. CDK6, SOX9, and EGFR, genes previously implicated in chordoma biology, are also recovered. We find genomic and transcriptomic features that predict specific dependencies, including interferon-stimulated gene expression, which correlates with ADAR dependence and is elevated in chordoma. Validating the therapeutic relevance of dependencies, small-molecule inhibitors of SHP2, encoded by PTPN11, have potent preclinical efficacy against chordoma. Our results generate an emerging map of chordoma dependencies to enable biological and therapeutic hypotheses.

Indexed as

Bone NeoplasmsChordomaApoptosis Regulatory ProteinsCell Line, TumorDNA-Binding ProteinsDNA HelicasesGene Expression ProfilingGenes, EssentialHumansTranscriptomeApoptosis Regulatory ProteinsDNA-Binding ProteinsDNA HelicasesFANCM protein, humanTHAP1 protein, human

Identifiers

PMID37024492
PMCPMC10079670
OpenAlexW4362663848

What OpenQuestion holds

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LicenceCC BY
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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.