Evidence map›Paper›PMID 26198537›Full record

ArticleJournal of translational medicine2015

Development of a multiparameter flow cytometric assay as a potential biomarker for homologous recombination deficiency in women with high-grade serous ovarian cancer.

Jung-Min Lee, Nicolas Gordon, Jane B Trepel, Min-Jung Lee, Minshu Yu, Elise C Kohn

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

Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 16 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Jung-Min LeeWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr. MSC1906, Building 10, Room 12N/226, Bethesda, MD, 20892-1906, USA. leej6@mail.nih.gov.
Nicolas GordonWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr. MSC1906, Building 10, Room 12N/226, Bethesda, MD, 20892-1906, USA. nick.gordon24@gmail.com.
Jane B TrepelDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA. jt66h@nih.gov.
Min-Jung LeeDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA. leemj@mail.nih.gov.
Minshu YuWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr. MSC1906, Building 10, Room 12N/226, Bethesda, MD, 20892-1906, USA. yum@intra.nci.nih.gov.
Elise C KohnWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr. MSC1906, Building 10, Room 12N/226, Bethesda, MD, 20892-1906, USA. kohne@mail.nih.gov.
Center for Cancer Research · USNational Cancer Institute · US

Funding

Targeting DNA damage repair and related pathways in HRD-womens cancersZIABC011525 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LEE, JUNG-MIN · 2013 to 2025
$14.8M
Intramural NIH HHS
6 · The paper itself

Abstract

objectivesPARP inhibitors (PARPi) are a novel class of drugs with activity in patients with acquired or germline homologous recombination (HR) deficiency-associated high-grade serous ovarian cancer (HGSOC). We hypothesized that measuring γH2AX as an indicator of DNA double-strand breaks (DSB), and MRE11 or RAD51 as an indicator of DSB repair, would reflect HR status and predict response to PARPi-based therapy. Our aim was to develop and use high-throughput multiparametric flow cytometry to quantify γH2AX with MRE11 or RAD51 in PBMCs as a readily available surrogate.

methodsHealthy donor PBMCs were used for assay development and optimization. We validated induction of γH2AX, MRE11 and RAD51 by staining with fluorophore-conjugated antibodies. The multiparameter flow cytometric method was applied to PBMC samples from recurrent HGSOC patients who were treated with PARPi, olaparib and carboplatin.

resultsStimulation was necessary for quantification of a DNA damage response to olaparib/carboplatin in healthy donor PBMCs. The flow cytometric protocol could not distinguish between cytoplasmic and nuclear RAD51, erroneously indicating activation in response to injury. Thus, MRE11 was selected as the marker of DSB repair. PBMCs from 15 recurrent HGSOC patients were then examined. Patients who did not respond to PARPi therapy had a significantly higher pre-treatment level of γH2AX (p = 0.01), and a higher ratio of γH2AX/MRE11 (11.0 [3.5-13.2] v. 3.3 [2.8-9.9], p < 0.03) compared with responders.

conclusionsWe successfully developed and applied a multiparameter flow cytometry assay to measure γH2AX and MRE11 in PBMCs. Prospective studies will be required to validate this surrogate biomarker assay as a potential predictive biomarker of PARPi-based therapy.

Indexed as

Homologous RecombinationAdultAgedBiomarkers, TumorCarboplatinDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA RepairFemaleFlow CytometryGene Expression Regulation, NeoplasticHistonesHumansLeukocytes, MononuclearMiddle AgedMRE11 Homologue ProteinBiomarkers, TumorCarboplatinDNA-Binding ProteinsH2AX protein, humanHistonesMRE11 Homologue ProteinMRE11 protein, humanolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsRAD51 protein, humanRad51 Recombinase

Identifiers

PMID26198537
PMCPMC4508767
OpenAlexW1959660762

What OpenQuestion holds

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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.