Evidence map›Paper›PMID 31618628›Full record

ArticleCell reports2019

Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses.

Thomas Botton, Eric Talevich, Vivek Kumar Mishra, Tongwu Zhang, A Hunter Shain, Céline Berquet, Alexander Gagnon, Robert L Judson, Robert Ballotti, Antoni Ribas and 6 more

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

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

60 citing papers in PubMed, 117 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Review
  5. Gene fusions in melanocytic lesions: an updated comprehensive review.Journal of pathology and translational medicine · 2026
    Article
  6. Article
  7. Article
  8. ACase reports in dermatological medicine · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Braf-Mutant Melanomas: Biology and Therapy.Current oncology (Toronto, Ont.) · 2024
    Review
  19. The mTOR pathway controls phosphorylation of BRAF at T401.Cell communication and signaling : CCS · 2024
    Article
  20. 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 8 institutions in 3 countries.

Thomas BottonHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA. Electronic address: thomas.botton@unice.fr.
Eric TalevichHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA.
Vivek Kumar MishraHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA.
Tongwu ZhangLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MA 20892, USA.
A Hunter ShainHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA.
Céline BerquetHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA.
Alexander GagnonHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA.
Robert L JudsonHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA.
Robert BallottiU1065, Institut National de la Santé et de la Recherche Médicale, Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, 06200 Nice, France.
Antoni RibasJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Meenhard HerlynMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Stéphane RocchiU1065, Institut National de la Santé et de la Recherche Médicale, Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, 06200 Nice, France.
Kevin M BrownLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MA 20892, USA.
Nicholas K HaywardOncogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Iwei YehHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA.
Boris C BastianHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA. Electronic address: boris.bastian@ucsf.edu.
UCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of California, San Francisco · USNational Cancer Institute · USCentre Méditerranéen de Médecine Moléculaire · FRInserm · FRQIMR Berghofer Medical Research Institute · AUThe Wistar Institute · USUniversity of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
TUMOR DEVELOPMENT AND PROGRESSION IN HUMAN MELANOCYTESP01CA025874 · NCI · WISTAR INSTITUTE · PI BASTIAN, BORIS C. · 1985 to 2015
$19.0M
Molecular and immunologic evolution of melanomas from pre-neoplastic lesionsR35CA220481 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASTIAN, BORIS C. · 2017 to 2023
$6.3M
Defining the role of SWI/SNF chromatin remodeling complex mutations during melanoma progressionK22CA217997 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHAIN, ALAN HUNTER · 2018 to 2021
$651k
NCI NIH HHS K22 CA217997NCI NIH HHS P01 CA025874NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA016042NCI NIH HHS R35 CA220481
6 · The paper itself

Abstract

BRAF fusions are detected in numerous neoplasms, but their clinical management remains unresolved. We identified six melanoma lines harboring BRAF fusions representative of the clinical cases reported in the literature. Their unexpected heterogeneous responses to RAF and MEK inhibitors could be categorized upon specific features of the fusion kinases. Higher expression level correlated with resistance, and fusion partners containing a dimerization domain promoted paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway and hyperproliferation in response to first- and second-generation RAF inhibitors. By contrast, next-generation αC-IN/DFG-OUT RAF inhibitors blunted paradoxical activation across all lines and had their therapeutic efficacy further increased in vitro and in vivo by combination with MEK inhibitors, opening perspectives in the clinical management of tumors harboring BRAF fusions.

Indexed as

AnimalsDimerizationDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMelanomaMiceMice, NudeMitogen-Activated Protein KinasesOncogene Proteins, FusionProtein IsoformsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafras ProteinsIntracellular Signaling Peptides and ProteinsMitogen-Activated Protein KinasesOncogene Proteins, FusionProtein IsoformsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafras ProteinsRNA, Small Interferingsrc kinase associated phosphoprotein 2VemurafenibBRAF fusionkinaseMEK inhibitormelanomaparadoxical activationpre-clinicalRAF inhibitorrearrangementsequencingtranslocation

Identifiers

PMID31618628
PMCPMC6939448
OpenAlexW2980620763

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.