Evidence map›Paper›PMID 23047548›Full record

ArticleBritish journal of cancer2012

Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer.

V Abkevich, K M Timms, B T Hennessy, J Potter, M S Carey, L A Meyer, K Smith-McCune, R Broaddus, K H Lu, J Chen and 10 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03462212 (A Randomized, Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib, Selected According to HRD Status, in Patients With Advanced), which is not on this map. Cited by 457 papers.

0numbers the graph read from it
0cells of the map it votes in
457citing papers in PubMed
8.2field-weighted citation impact, top 2% 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.

NCT03462212 phase1 / phase2unknown statusnot on this mapstarted 2021, after this paper: background citation

A Randomized, Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib, Selected According to HRD Status, in Patients With Advanced (Stage III B-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube Cancer Preceded by a Phase I Dose Escalation Study on Rucaparib-Bevacizumab Combination

TypeinterventionalSponsorFondazione Policlinico Universitario Agostino Gemelli IRCCSRan2021 to 2025Enrolled290ConditionsAdvanced (Stage IIIB-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube CancerArmsCarboplatin, Paclitaxel, Bevacizumab, Rucaparib
3 · Its place in the literature

Who cites it

457 citing papers in PubMed, 837 citations in OpenAlex.

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  5. RNASEH2B loss and PARP inhibition in advanced prostate cancer.The Journal of clinical investigation · 2024
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  6. [BRCA-like breast cancer patients benefit from cisplatin plus veliparib-results from the S1416 phase II study].Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023
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397 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

20 authors at 8 institutions in 3 countries.

V AbkevichMyriad Genetics Inc., Salt Lake City, UT, USA.
K M Timms
B T Hennessy
J Potter
M S Carey
L A Meyer
K Smith-McCune
R Broaddus
K H Lu
J Chen
T V Tran
D Williams
D Iliev
S Jammulapati
L M FitzGerald
T Krivak
J A DeLoia
A Gutin
G B Mills
J S Lanchbury
Myriad Genetics · USThe University of Texas MD Anderson Cancer Center · USUniversity of British Columbia · CABeaumont Hospital · IEGeorge Washington University · USThe University of Texas at Austin · USUniversity of California, San Francisco · USUniversity of Pittsburgh · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
UNIVERSITY OF TEXAS MD ANDERSON SPORE IN OVARIAN CANCERP50CA083639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BAST, ROBERT C · 1999 to 2015
$33.0M
Targeting the PI3K Signaling Pathway in Endometrial CarcinomaP50CA098258 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BODURKA, DIANE · 2003 to 2020
$32.0M
Training of Academic Gynecologic OncologistsT32CA101642 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ANIL K SOOD, Kathleen Schmeler · 2005 to 2026
$9.2M
NCI NIH HHS CA016672NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA083639NCI NIH HHS P50 CA098258NCI NIH HHS P50CA83639NCI NIH HHS T32 CA101642NCI NIH HHS T32-CA101642PHS HHS NCI 64602
6 · The paper itself

Abstract

backgroundDefects in BRCA1, BRCA2, and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of loss of heterozygosity (LOH).

methodsOvarian tumours from two independent data sets were characterised for defects in BRCA1, BRCA2, and RAD51C, and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines.

resultsLoss of heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 (P=10(-11)). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets (P=10(-5) and 10(-29)), and identified breast and pancreatic cell lines with BRCA defects.

conclusionThe HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers.

Indexed as

Loss of HeterozygosityRecombinational DNA RepairAdultAgedAged, 80 and overBRCA1 ProteinBRCA2 ProteinCarcinoma, Ovarian EpithelialCell Line, TumorCohort StudiesDisease-Free SurvivalDNA-Binding ProteinsDNA Breaks, Double-StrandedFemaleHumansMiddle AgedBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanDNA-Binding ProteinsRAD51C protein, human

Identifiers

PMID23047548
PMCPMC3493866
OpenAlexW2074952360

What OpenQuestion holds

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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.