Evidence map›Paper›PMID 32203465›Full record

ArticleNature genetics2020

Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma.

David J H Shih, Naema Nayyar, Ivanna Bihun, Ibiayi Dagogo-Jack, Corey M Gill, Elisa Aquilanti, Mia Bertalan, Alexander Kaplan, Megan R D'Andrea, Ugonma Chukwueke and 33 more

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

Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
198citing papers in PubMed, 2 pooled it
15.3field-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

198 citing papers in PubMed, 2 syntheses or guidelines pooled it, 294 citations in OpenAlex.

  1. Pooled it
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  10. Survival of lung cancer patients with central nervous system metastases: from clinical trials to mouse models.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
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  16. Therapeutic advances with KRASCancer gene therapy · 2026
    Review
  17. Article
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  20. Article

138 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors at 7 institutions in 3 countries.

David J H Shih *Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9802-4937
Naema Nayyar *Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3436-8404
Ivanna BihunBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
Ibiayi Dagogo-JackDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Corey M GillDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4494-1948
Elisa AquilantiBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
Mia BertalanDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Alexander KaplanDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Megan R D'AndreaDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7371-4739
Ugonma ChukwuekeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Franziska Maria IppenDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Christopher Alvarez-BreckenridgeDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
Nicholas D CamardaDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1853-0056
Matthew LastrapesDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Devin McCabeDepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2183-4368
Ben KuterDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Benjamin KaufmanBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
Matthew R StricklandDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Juan Carlos Martinez-GutierrezDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Deepika NagabhushanDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Magali De SauvageDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9486-945X
Michael D WhiteDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Brandyn A CastroDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Kaitlin HoangDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Andrew KanebDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Emily D BatchelorDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Sun Ha PaekDepartment of Neurosurgery, Seoul National University College of Medicine, Seoul, South Korea.ORCID http://orcid.org/0000-0003-3007-8653
Sun Hye ParkDepartment of Neurosurgery, Seoul National University College of Medicine, Seoul, South Korea.
Maria Martinez-LageDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Anna S BerghoffDepartment of Medicine I, Division of Oncology, Medical University of Vienna, Comprehensive Cancer Center Vienna, Vienna, Austria.
Parker MerrillDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5025-7152
Elizabeth R GerstnerDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Tracy T BatchelorDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Matthew P FroschDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Ryan P FrazierDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Darrell R BorgerDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
A John IafrateDepartment of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Bruce E JohnsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sandro SantagataDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7528-9668
Matthias PreusserDepartment of Medicine I, Division of Oncology, Medical University of Vienna, Comprehensive Cancer Center Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-3541-2315
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
Scott L CarterDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. carter.scott@jimmy.harvard.edu.ORCID http://orcid.org/0000-0002-8480-1475
Priscilla K BrastianosBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. pbrastianos@mgh.harvard.edu.ORCID http://orcid.org/0000-0003-4470-8425
Massachusetts General Hospital · USBroad Institute · USBrigham and Women's Hospital · USComprehensive Cancer Center Vienna · ATDana-Farber Cancer Institute · USSeoul National University · KRHarvard University · US

Funding

Identification of genomic drivers of brain metastases in lung adenocarcinomaR01CA227156 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, CARTER, SCOTT · 2018 to 2022
$3.5M
CIHRNCI NIH HHS R01 CA227156
6 · The paper itself

Abstract

Brain metastases from lung adenocarcinoma (BM-LUAD) frequently cause patient mortality. To identify genomic alterations that promote brain metastases, we performed whole-exome sequencing of 73 BM-LUAD cases. Using case-control analyses, we discovered candidate drivers of brain metastasis by identifying genes with more frequent copy-number aberrations in BM-LUAD compared to 503 primary LUADs. We identified three regions with significantly higher amplification frequencies in BM-LUAD, including MYC (12 versus 6%), YAP1 (7 versus 0.8%) and MMP13 (10 versus 0.6%), and significantly more frequent deletions in CDKN2A/B (27 versus 13%). We confirmed that the amplification frequencies of MYC, YAP1 and MMP13 were elevated in an independent cohort of 105 patients with BM-LUAD. Functional assessment in patient-derived xenograft mouse models validated the notion that MYC, YAP1 or MMP13 overexpression increased the incidence of brain metastasis. These results demonstrate that somatic alterations contribute to brain metastases and that genomic sequencing of a sufficient number of metastatic tumors can reveal previously unknown metastatic drivers.

Indexed as

Adenocarcinoma of LungAnimalsBrain NeoplasmsCase-Control StudiesCell LineDNA Copy Number VariationsExome SequencingFemaleGenes, mycGenomicsHEK293 CellsHumansLung NeoplasmsMaleMatrix Metalloproteinase 13MiceMatrix Metalloproteinase 13Transcription Factors

Identifiers

PMID32203465
PMCPMC7136154
OpenAlexW3012749684

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.