Evidence map›Paper›PMID 29617664›Full record

ArticleCell reports2018

Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas.

Theo A Knijnenburg, Linghua Wang, Michael T Zimmermann, Nyasha Chambwe, Galen F Gao, Andrew D Cherniack, Huihui Fan, Hui Shen, Gregory P Way, Casey S Greene and 29 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05372081 (Clinical and Molecular Study With Digital Support of Patients With Inoperable Lung Cancer), which is not on this map. Cited by 708 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
708citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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.

NCT05372081 completednot on this mapstarted 2022, after this paper: background citation

Clinical and Molecular Study With Digital Support of Patients With Inoperable Lung Cancer

TypeobservationalSponsorHellenic Cooperative Oncology GroupRan2022 to 2025Enrolled200ConditionsNon-Small Cell Carcinoma of Lung, TNM Stage 4ArmsDigital platform
3 · Its place in the literature

Who cites it

708 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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  16. Prognostic implications of tissue-based homologous recombination deficiency in metastatic gastric cancer treated with immune checkpoint inhibitor plus chemotherapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
    Article
  17. Review
  18. Article
  19. Article
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648 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

39 authors.

Theo A KnijnenburgInstitute for Systems Biology, Seattle, WA 98109, USA.
Linghua WangDepartment of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Michael T ZimmermannGenomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA; Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Nyasha ChambweInstitute for Systems Biology, Seattle, WA 98109, USA.
Galen F GaoThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Andrew D CherniackThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
Huihui FanCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Hui ShenCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Gregory P WayDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19103, USA.
Casey S GreeneDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19103, USA.
Yuexin LiuDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rehan AkbaniDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Bin FengTESARO Inc., Waltham, MA 02451, USA.
Lawrence A DonehowerDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Chase MillerHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Yang ShenDepartment of Electrical and Computer Engineering, 3128 TAMU, Texas A&M University, College Station, TX 77843, USA.
Mostafa KarimiDepartment of Electrical and Computer Engineering, 3128 TAMU, Texas A&M University, College Station, TX 77843, USA.
Haoran ChenDepartment of Electrical and Computer Engineering, 3128 TAMU, Texas A&M University, College Station, TX 77843, USA.
Pora KimCenter for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Peilin JiaCenter for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Eve ShinbrotHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Shaojun ZhangDepartment of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Jianfang LiuChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA.
Hai HuChan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA.
Matthew H BaileyDivision of Oncology, Department of Medicine, Washington University, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63110, USA.
Christina YauUniversity of California, San Francisco, San Francisco, CA 94115, USA; Buck Institute for Research on Aging, Novato, CA 94945, USA.
Denise WolfUniversity of California, San Francisco, San Francisco, CA 94115, USA.
Zhongming ZhaoCenter for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
John N WeinsteinDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lei LiDepartment of Experimental Radiation Oncology, University of Texas MD Anderson Cancer, Houston, TX 77030, USA.
Li DingDivision of Oncology, Department of Medicine, Washington University, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63110, USA; Department of Genetics, Washington University, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University, St. Louis, MO 63110, USA.
Gordon B MillsDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Peter W LairdCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
David A WheelerHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Ilya ShmulevichInstitute for Systems Biology, Seattle, WA 98109, USA.
Cancer Genome Atlas Research Network
Raymond J MonnatDepartments of Pathology & Genome Sciences, University of Washington, Seattle, WA 98195-7705, USA. Electronic address: monnat@u.washington.edu.
Yonghong XiaoTESARO Inc., Waltham, MA 02451, USA. Electronic address: yxiao@genospace.com.
Chen WangDepartment of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA; Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: wang.chen@mayo.edu.

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7M
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI Zhenkun Lou · 2009 to 2026
$37.0M
Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3M
Tumor mutation signaturesP01CA077852 · NCI · UNIVERSITY OF WASHINGTON · PI MONNAT, RAYMOND J · 1999 to 2019
$26.0M
Gene Expression Patterns in Human Tumors Identified Using Transcript SequencingU24CA143848 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAYES, DAVID N, PEROU, CHARLES M · 2009 to 2016
$20.8M
Genome Characterization Center (GCC)U24CA143867 · NCI · BROAD INSTITUTE, INC. · PI GABRIEL, STACEY, MEYERSON, MATTHEW L. · 2009 to 2016
$17.0M
The Cancer Genome Atlas Data Analysis CenterU24CA143845 · NCI · BROAD INSTITUTE, INC. · PI CHIN, LYNDA, GETZ, GAD A · 2009 to 2016
$16.0M
Harvard Genome Characterization CenterU24CA144025 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHERLAPATI, RAJU S. · 2009 to 2016
$14.0M
The USC-JHU Cancer Epigenome Characterization CenterU24CA143882 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BAYLIN, STEPHEN B., WEISENBERGER, DANIEL JOSEPH · 2009 to 2016
$13.3M
NCI NIH HHS P01 CA077852NCI NIH HHS P01 CA193124NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA136393NCI NIH HHS R01 CA163722NCI NIH HHS R01 CA190635NCI NIH HHS R50 CA221675NCI NIH HHS U01 CA176303NCI NIH HHS U01 CA217883NCI NIH HHS U24 CA143799NCI NIH HHS U24 CA143835NCI NIH HHS U24 CA143840NCI NIH HHS U24 CA143843NCI NIH HHS U24 CA143845NCI NIH HHS U24 CA143848NCI NIH HHS U24 CA143858NCI NIH HHS U24 CA143866NCI NIH HHS U24 CA143867NCI NIH HHS U24 CA143882NCI NIH HHS U24 CA143883NCI NIH HHS U24 CA144025NCI NIH HHS U24 CA210949NCI NIH HHS U24 CA210950NCI NIH HHS U24 CA210957NCI NIH HHS U24 CA210990NHGRI NIH HHS T32 HG000046NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NIEHS NIH HHS P30 ES013508NIGMS NIH HHS R35 GM124952NLM NIH HHS R01 LM012806
6 · The paper itself

Abstract

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy.

Indexed as

Genome, HumanRecombinational DNA RepairCell Line, TumorDNA DamageGene SilencingHumansLoss of HeterozygosityMachine LearningMutationNeoplasmsTumor Suppressor ProteinsTumor Suppressor ProteinsDNA damage footprintsDNA damage repairepigenetic silencingintegrative statistical analysismutational signaturesprotein structure analysissomatic copy-number alterationssomatic mutationsThe Cancer Genome Atlas PanCanAtlas project

Identifiers

PMID29617664
PMCPMC5961503

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Registered trials

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.