Evidence map›Paper›PMID 33462368›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2021

Homologous recombination deficiency (HRD) score in germline BRCA2- versus ATM-altered prostate cancer.

Tamara L Lotan, Harsimar B Kaur, Daniela C Salles, Sanjana Murali, Edward M Schaeffer, Jerry S Lanchbury, William B Isaacs, Robert Brown, Andrea L Richardson, Olivier Cussenot and 3 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01221168 (ProGene), which is not on this map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
11.1field-weighted citation impact, top 1% 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.

NCT01221168 recruitingnot on this map

ProGene: Etude Genetique et Epidemiologique du Cancer de la Prostate Familial

TypeobservationalSponsorCentre de Recherche sur les Pathologies ProstatiquesRan1996 to 2026Enrolled10,000ConditionsProstate Cancer
3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.

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  9. Contemporary review of prognostic markers of prostate cancer from a pathologist perspective.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025
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3 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

13 authors at 5 institutions in 3 countries.

Tamara L LotanDepartment of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA. tlotan1@jhmi.edu.
Harsimar B KaurDepartment of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-1178-7596
Daniela C SallesDepartment of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-1904-185X
Sanjana MuraliDepartment of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Edward M SchaefferDepartment of Urology, Northwestern University, Chicago, IL, USA.
Jerry S LanchburyMyriad Genetics, Salt Lake City, UT, USA.
William B IsaacsDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Robert BrownDivision of Cancer and Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK.
Andrea L RichardsonDepartment of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Olivier CussenotDepartment of Urology and Predictive Onco-Urology Group, APHP-Sorbonne University, Paris, France.
Geraldine Cancel-TassinDepartment of Urology and Predictive Onco-Urology Group, APHP-Sorbonne University, Paris, France.
Kirsten M TimmsMyriad Genetics, Salt Lake City, UT, USA.
Emmanuel S AntonarakisDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. eantona1@jhmi.edu.ORCID http://orcid.org/0000-0003-0031-9655
Johns Hopkins University · USMyriad Genetics · USSorbonne Université · FRNorthwestern University · USOvarian Cancer Action · GB

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
Cancer Research UK 13086NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236
6 · The paper itself

Abstract

The homologous recombination deficiency (HRD) score integrates three DNA-based measures of genomic instability, and has been understudied in prostate cancer. Given the recent FDA approval of two PARP inhibitors for prostate cancer, HRD score analysis could help to refine treatment selection. We assessed HRD score (defined as the sum of loss-of-heterozygosity, telomeric allelic imbalance, and large-scale state transitions) in three cohorts of primary prostate cancer, including a Johns Hopkins University (JHU) cohort with germline mutations in BRCA2, ATM, or CHEK2 (n = 64), the TCGA cohort (n = 391), and the PROGENE cohort (n = 102). In the JHU cohort, tumors with germline BRCA2 mutations had higher HRD scores (median = 27) than those with germline ATM or CHEK2 mutations (median = 16.5 [p = 0.029] and 9 [p < 0.001], respectively). For TCGA tumors without underlying HR pathway mutations, the median HRD score was 11, significantly lower than ovarian carcinoma lacking BRCA1/2 mutations (median = 28). In the absence of HR gene mutations, the median HRD score was unexpectedly higher among prostate cancers with TP53 mutations versus those without (17 vs. 11; p = 0.015); this finding was confirmed in the PROGENE cohort (24 vs. 16; p = 0.001). Finally, among eight BRCA2-altered patients who received olaparib, progression-free survival trended longer in those with HRD scores above versus below the median (14.9 vs. 9.9 months). We conclude that HRD scores are low in primary prostate cancer and higher in cases with germline BRCA2 or somatic TP53 mutations. Germline BRCA2-altered cases have significantly higher HRD scores than germline ATM-altered or CHEK2-altered cases, consistent with the lower efficacy of PARP inhibitors among the latter.

Indexed as

AdultAgedAllelic ImbalanceAtaxia Telangiectasia Mutated ProteinsBiomarkers, TumorBRCA2 ProteinGenomic InstabilityGerm-Line MutationHumansLoss of HeterozygosityMaleMiddle AgedProstatic NeoplasmsAtaxia Telangiectasia Mutated ProteinsATM protein, humanBiomarkers, TumorBRCA2 ProteinBRCA2 protein, human

Identifiers

PMID33462368
PMCPMC8154637
OpenAlexW3122971575

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.