Evidence map›Paper›PMID 26015868›Full record

ArticleBiomarker research2015

Pan-cancer analysis of genomic scar signatures associated with homologous recombination deficiency suggests novel indications for existing cancer drugs.

Andrea M Marquard, Aron C Eklund, Tejal Joshi, Marcin Krzystanek, Francesco Favero, Zhigang C Wang, Andrea L Richardson, Daniel P Silver, Zoltan Szallasi, Nicolai J Birkbak

Open access · goldAbstract read
In one paragraph

Article in Biomarker research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
183citing papers in PubMed, 1 pooled it
5.0field-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

183 citing papers in PubMed, 1 synthesis or guideline pooled it, 317 citations in OpenAlex.

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123 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

10 authors at 3 institutions in 2 countries.

Andrea M Marquard *Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 8, 2800 Lyngby, Denmark.
Aron C Eklund *Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 8, 2800 Lyngby, Denmark.
Tejal JoshiCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 8, 2800 Lyngby, Denmark.
Marcin KrzystanekCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 8, 2800 Lyngby, Denmark.
Francesco FaveroCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 8, 2800 Lyngby, Denmark.
Zhigang C WangDepartment of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, 02215 Boston, Massachusetts USA.
Andrea L RichardsonDepartment of Pathology, Brigham and Women's Hospital, 75 Francis Street, 02115 Boston, Massachusetts USA.
Daniel P SilverDepartment of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, 02215 Boston, Massachusetts USA.
Zoltan SzallasiCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 8, 2800 Lyngby, Denmark.
Nicolai J BirkbakCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 8, 2800 Lyngby, Denmark.
Technical University of Denmark · DKDana-Farber Cancer Institute · USBrigham and Women's Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOvarian and triple-negative breast cancers with BRCA1 or BRCA2 loss are highly sensitive to treatment with PARP inhibitors and platinum-based cytotoxic agents and show an accumulation of genomic scars in the form of gross DNA copy number aberrations. Cancers without BRCA1 or BRCA2 loss but with accumulation of similar genomic scars also show increased sensitivity to platinum-based chemotherapy. Therefore, reliable biomarkers to identify DNA repair-deficient cancers prior to treatment may be useful for directing patients to platinum chemotherapy and possibly PARP inhibitors. Recently, three SNP array-based signatures of chromosomal instability were published that each quantitate a distinct type of genomic scar considered likely to be caused by improper DNA repair. They measure telomeric allelic imbalance (named NtAI), large scale transition (named LST), and loss of heterozygosity (named HRD-LOH), and it is suggested that these signatures may act as biomarkers for the state of DNA repair deficiency in a given cancer.

resultsWe explored the pan-cancer distribution of scores of the three signatures utilizing a panel of 5371 tumors representing 15 cancer types from The Cancer Genome Atlas, and found a good correlation between scores of the three signatures (Spearman's ρ 0.73-0.87). In addition we found that cancer types ordinarily receiving platinum as standard of care have higher median scores of all three signatures. Interestingly, we also found that smaller subpopulations of high-scoring tumors exist in most cancer types, including those for which platinum chemotherapy is not standard therapy.

conclusionsWithin several cancer types that are not ordinarily treated with platinum chemotherapy, we identified tumors with high levels of the three genomic biomarkers. These tumors represent identifiable subtypes of patients which may be strong candidates for clinical trials with PARP inhibitors or platinum-based chemotherapeutic regimens.

Indexed as

CancerGenomic scarsHomologous recombination deficiency

Identifiers

PMID26015868
PMCPMC4443545
OpenAlexW2120897875

What OpenQuestion holds

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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.