Evidence map›Paper›PMID 28658208›Full record

ArticleNature2017

Recurrent and functional regulatory mutations in breast cancer.

Esther Rheinbay, Prasanna Parasuraman, Jonna Grimsby, Grace Tiao, Jesse M Engreitz, Jaegil Kim, Michael S Lawrence, Amaro Taylor-Weiner, Sergio Rodriguez-Cuevas, Mara Rosenberg and 23 more

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

Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed, 2 pooled it
20.6field-weighted citation impact, top 1% 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

169 citing papers in PubMed, 2 syntheses or guidelines pooled it, 316 citations in OpenAlex.

  1. Pooled it
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  7. Crosstalk BetweenCancers · 2026
    Review
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  9. A class of COPI cargo receptors regulates processing of transmembrane proteins by reinforcing their Golgi retention.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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109 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 7 institutions in 3 countries.

Esther RheinbayThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Prasanna ParasuramanMassachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
Jonna GrimsbyThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Grace TiaoThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Jesse M EngreitzThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Jaegil KimThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Michael S LawrenceThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Amaro Taylor-WeinerThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Sergio Rodriguez-CuevasInstituto de Enfermedades de la Mama FUCAM, A.C., Mexico City 04980, Mexico.
Mara RosenbergThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Julian HessThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Chip StewartThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Yosef E MaruvkaThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Petar StojanovThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Maria L CortesThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Sara SeepoThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Carrie CibulskisThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Adam TracyThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Trevor J PughPrincess Margaret Cancer Centre, University Health Network and the Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Jesse LeeMassachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
Zongli ZhengMassachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
Leif W EllisenMassachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
A John IafrateMassachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
Jesse S BoehmThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Stacey B GabrielThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Matthew MeyersonThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Todd R GolubThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Jose BaselgaHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Alfredo Hidalgo-MirandaInstituto Nacional de Medicina Genómica, Mexico City 14610, Mexico.
Toshi ShiodaMassachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
Andre BernardsMassachusetts General Hospital Center for Cancer Research, Charlestown, Massachusetts 02129, USA.
Eric S LanderThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Gad GetzThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Broad Institute · USCenter for Cancer Research · USMassachusetts General Hospital · USHarvard University · USMemorial Sloan Kettering Cancer Center · USNational Institute of Genomic Medicine · MXUniversity Health Network · CA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients.

Indexed as

MutationBreast NeoplasmsCohort StudiesE2F Transcription FactorsExomeGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-alphaHigh-Throughput Nucleotide SequencingHumansPromoter Regions, GeneticProtein BindingReceptors, EstrogenRNA, Long NoncodingE2F Transcription FactorsFOXA1 protein, humanHepatocyte Nuclear Factor 3-alphaNEAT1 long non-coding RNA, humanReceptors, EstrogenRMRP non-coding RNA, humanRNA, Long Noncoding

Identifiers

PMID28658208
PMCPMC5563978
OpenAlexW2724571272

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.