Evidence map›Paper›PMID 27760319›Full record

ArticleCell reports2016

Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants.

Lisa Brenan, Aleksandr Andreev, Ofir Cohen, Sasha Pantel, Atanas Kamburov, Davide Cacchiarelli, Nicole S Persky, Cong Zhu, Mukta Bagul, Eva M Goetz and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
9.6field-weighted citation impact, top 2% 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

90 citing papers in PubMed, 168 citations in OpenAlex.

  1. Article
  2. ERK autoinhibition mechanism informs a drug combination strategy.Protein science : a publication of the Protein Society · 2026
    Article
  3. Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

30 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

17 authors at 3 institutions in 1 country.

Lisa BrenanThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Aleksandr AndreevThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ofir CohenThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Sasha PantelThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Atanas KamburovThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Davide CacchiarelliThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Nicole S PerskyThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cong ZhuThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mukta BagulThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Eva M GoetzThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Alex B BurginThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Levi A GarrawayThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Gad GetzThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Tarjei S MikkelsenThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Federica PiccioniThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
David E RootThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cory M JohannessenThe Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: johannes@broadinstitute.org.
Broad Institute · USDana-Farber Cancer Institute · USHarvard University · US

Funding

The Cancer Genome Atlas Data Analysis CenterU24CA143845 · NCI · BROAD INSTITUTE, INC. · PI CHIN, LYNDA, GETZ, GAD A · 2009 to 2016
$16.0M
NCI NIH HHS U24 CA143845
6 · The paper itself

Abstract

Tumor-specific genomic information has the potential to guide therapeutic strategies and revolutionize patient treatment. Currently, this approach is limited by an abundance of disease-associated mutants whose biological functions and impacts on therapeutic response are uncharacterized. To begin to address this limitation, we functionally characterized nearly all (99.84%) missense mutants of MAPK1/ERK2, an essential effector of oncogenic RAS and RAF. Using this approach, we discovered rare gain- and loss-of-function ERK2 mutants found in human tumors, revealing that, in the context of this assay, mutational frequency alone cannot identify all functionally impactful mutants. Gain-of-function ERK2 mutants induced variable responses to RAF-, MEK-, and ERK-directed therapies, providing a reference for future treatment decisions. Tumor-associated mutations spatially clustered in two ERK2 effector-recruitment domains yet produced mutants with opposite phenotypes. This approach articulates an allele-characterization framework that can be scaled to meet the goals of genome-guided oncology.

Indexed as

Cell Line, TumorDrug Resistance, NeoplasmDual Specificity Phosphatase 6HumansMitogen-Activated Protein Kinase 1Models, MolecularMutation, MissensePhenotypePhosphorylationProtein Kinase InhibitorsReproducibility of ResultsDual Specificity Phosphatase 6DUSP6 protein, humanMitogen-Activated Protein Kinase 1Protein Kinase InhibitorscancerERKfunctional biologyMAPKprecision medicineprecision oncologyrare mutants

Identifiers

PMID27760319
PMCPMC5120861
OpenAlexW2535595233

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.