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

Overview of attention for article published in Journal of Translational Medicine, July 2015
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Title
Development of a multiparameter flow cytometric assay as a potential biomarker for homologous recombination deficiency in women with high-grade serous ovarian cancer
Published in
Journal of Translational Medicine, July 2015
DOI 10.1186/s12967-015-0604-z
Pubmed ID
Authors

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

Abstract

PARP 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. Healthy 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. Stimulation 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. We 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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 27%
Student > Master 3 27%
Researcher 2 18%
Professor > Associate Professor 1 9%
Unknown 2 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 27%
Medicine and Dentistry 2 18%
Psychology 1 9%
Agricultural and Biological Sciences 1 9%
Unknown 4 36%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 July 2015.
All research outputs
#2,858,010
of 5,382,699 outputs
Outputs from Journal of Translational Medicine
#833
of 1,512 outputs
Outputs of similar age
#104,068
of 190,035 outputs
Outputs of similar age from Journal of Translational Medicine
#87
of 105 outputs
Altmetric has tracked 5,382,699 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,512 research outputs from this source. They receive a mean Attention Score of 4.1. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 190,035 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 105 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.