Evidence map›Paper›PMID 28454577›Full record

ArticleMolecular cancer2017

The landscape of BRAF transcript and protein variants in human cancer.

Andrea Marranci, Zhijie Jiang, Marianna Vitiello, Elena Guzzolino, Laura Comelli, Samanta Sarti, Simone Lubrano, Cinzia Franchin, Ileabett Echevarría-Vargas, Andrea Tuccoli and 13 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

23 citing papers in PubMed, 51 citations in OpenAlex.

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  20. Systemic therapy for brain metastases.Critical reviews in oncology/hematology · 2019
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 9 institutions in 2 countries.

Andrea MarranciOncogenomics Unit, Core Research Laboratory, Istituto Toscano Tumori (ITT), AOUP, CNR-IFC, Via Moruzzi 1, 56124, Pisa, Italy.
Zhijie JiangCenter for Computational Science, University of Miami, Gables One Tower, Room 600 N, 1320 S. Dixie Highway, Coral Gables, FL, 33146-2926, USA.
Marianna VitielloOncogenomics Unit, Core Research Laboratory, Istituto Toscano Tumori (ITT), AOUP, CNR-IFC, Via Moruzzi 1, 56124, Pisa, Italy.
Elena GuzzolinoScuola Superiore Sant'Anna, Pisa, Italy.
Laura ComelliInstitute of Clinical Physiology (IFC), CNR, Via Moruzzi 1, 56124, Pisa, Italy.
Samanta SartiOncogenomics Unit, Core Research Laboratory, Istituto Toscano Tumori (ITT), AOUP, CNR-IFC, Via Moruzzi 1, 56124, Pisa, Italy.
Simone LubranoOncogenomics Unit, Core Research Laboratory, Istituto Toscano Tumori (ITT), AOUP, CNR-IFC, Via Moruzzi 1, 56124, Pisa, Italy.
Cinzia FranchinDepartment of Biomedical Sciences, University of Padova, Padova, Italy.
Ileabett Echevarría-VargasMolecular and Cellular Oncogenesis Program & Melanoma Research Center, The Wistar Institute, Philadelphia, USA.
Andrea TuccoliOncogenomics Unit, Core Research Laboratory, Istituto Toscano Tumori (ITT), AOUP, CNR-IFC, Via Moruzzi 1, 56124, Pisa, Italy.
Alberto MercatantiInstitute of Clinical Physiology (IFC), CNR, Via Moruzzi 1, 56124, Pisa, Italy.
Monica EvangelistaInstitute of Clinical Physiology (IFC), CNR, Via Moruzzi 1, 56124, Pisa, Italy.
Paolo SportolettiInstitute of Hematology, University of Perugia, Perugia, Italy.
Giorgio CozzaDepartment of Molecular Medicine, University of Padova, Padova, Italy.
Ettore LuziDepartment of Surgery and Translational Medicine, University of Firenze, Firenze, Italy.
Enrico CapobiancoCenter for Computational Science, University of Miami, Gables One Tower, Room 600 N, 1320 S. Dixie Highway, Coral Gables, FL, 33146-2926, USA.
Jessie VillanuevaMolecular and Cellular Oncogenesis Program & Melanoma Research Center, The Wistar Institute, Philadelphia, USA.
Giorgio ArrigoniDepartment of Biomedical Sciences, University of Padova, Padova, Italy.
Giovanni SignoreIIT@NEST, Center for Nanotechnology Innovation, Pisa, Italy.
Silvia RocchiccioliInstitute of Clinical Physiology (IFC), CNR, Via Moruzzi 1, 56124, Pisa, Italy.
Letizia PittoInstitute of Clinical Physiology (IFC), CNR, Via Moruzzi 1, 56124, Pisa, Italy.
Nicholas TsinoremasCenter for Computational Science, University of Miami, Gables One Tower, Room 600 N, 1320 S. Dixie Highway, Coral Gables, FL, 33146-2926, USA. ntsinoremas@med.miami.edu.
Laura PolisenoOncogenomics Unit, Core Research Laboratory, Istituto Toscano Tumori (ITT), AOUP, CNR-IFC, Via Moruzzi 1, 56124, Pisa, Italy. laura.poliseno@gmail.com.ORCID 0000-0001-6557-955X
Istituto di Fisiologia Clinica · ITUniversity of Miami · USUniversity of Padua · ITUniversity of Siena · ITThe Wistar Institute · USCenter for Nanotechnology Innovation · ITScuola Superiore Sant'Anna · ITUniversity of Florence · ITUniversity of Perugia · IT

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Aaron Robert Goldman · 1985 to 2026
$75.9M
TRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$15.3M
Molecular approaches to overcome intrinsic drug resistance in BRAF and NRAS-mutanK01CA175269 · NCI · WISTAR INSTITUTE · PI VILLANUEVA, JESSIE · 2013 to 2017
$754k
NCI NIH HHS K01 CA175269NCI NIH HHS P30 CA010815NCI NIH HHS T32 CA009171
6 · The paper itself

Abstract

backgroundThe BRAF protein kinase is widely studied as a cancer driver and therapeutic target. However, the regulation of its expression is not completely understood.

resultsTaking advantage of the RNA-seq data of more than 4800 patients belonging to 9 different cancer types, we show that BRAF mRNA exists as a pool of 3 isoforms (reference BRAF, BRAF-X1, and BRAF-X2) that differ in the last part of their coding sequences, as well as in the length (BRAF-ref: 76 nt; BRAF-X1 and BRAF-X2: up to 7 kb) and in the sequence of their 3'UTRs. The expression levels of BRAF-ref and BRAF-X1/X2 are inversely correlated, while the most prevalent among the three isoforms varies from cancer type to cancer type. In melanoma cells, the X1 isoform is expressed at the highest level in both therapy-naïve cells and cells with acquired resistance to vemurafenib driven by BRAF gene amplification or expression of the Δ[3-10] splicing variant. In addition to the BRAF-ref protein, the BRAF-X1 protein (the full length as well as the Δ[3-10] variant) is also translated. The expression levels of the BRAF-ref and BRAF-X1 proteins are similar, and together they account for BRAF functional activities. In contrast, the endogenous BRAF-X2 protein is hard to detect because the C-terminal domain is selectively recognized by the ubiquitin-proteasome pathway and targeted for degradation.

conclusionsBy shedding light on the repertoire of BRAF mRNA and protein variants, and on the complex regulation of their expression, our work paves the way to a deeper understanding of a crucially important player in human cancer and to a more informed development of new therapeutic strategies.

Indexed as

Alternative SplicingCell Line, TumorDrug Resistance, NeoplasmExonsGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansIndolesMelanomaNeoplasmsProtein IsoformsProto-Oncogene Proteins B-rafRNA, MessengerSulfonamidesVemurafenibBRAF protein, humanIndolesProtein IsoformsProto-Oncogene Proteins B-rafRNA, MessengerSulfonamidesVemurafenibBRAFExon-spanning readsMelanomaProtein variantsRNA-sequencingTranscript variants

Identifiers

PMID28454577
PMCPMC5410044
OpenAlexW2609841933

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.