Evidence map›Paper›PMID 41871940›Full record

ArticleThe oncologist2026

Homologous recombination deficiency and genomic alterations in advanced prostate cancer: insights for precision therapy.

Chiara Mercinelli, Dean Pavlick, Neeraj Agarwal, Philippe E Spiess, Roger Li, Ashish M Kamat, Petros Grivas, Shilpa Gupta, Brigida Anna Maiorano, Valentina Tateo and 7 more

Abstract read
In one paragraph

Article in The oncologist, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Chiara MercinelliVita-Salute San Raffaele University, Via Olgettina 60, Milan, 20132, Italy.ORCID 0000-0003-1165-1776
Dean PavlickFoundation Medicine Inc, Cambridge, MA, 02141-2115, United States.ORCID 0000-0001-6075-6246
Neeraj AgarwalDepartment of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, United States.ORCID 0000-0003-1076-0428
Philippe E SpiessDepartment of Genito-Urinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, United States.ORCID 0000-0002-5723-1972
Roger LiDepartment of Genito-Urinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, United States.
Ashish M KamatDepartment of Urology, MD Anderson Cancer Center, Houston, TX, 77030, United States.
Petros GrivasFred Hutchinson Cancer Center, University of Washington, Seattle, WA, 98109, United States.
Shilpa GuptaCleveland Clinic Taussig Cancer Institute, Cleveland, OH, 44195, United States.ORCID 0000-0002-8775-503X
Brigida Anna MaioranoDepartment of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Via Olgettina 60, 20132, Milan, Italy.ORCID 0000-0001-5423-3158
Valentina TateoDepartment of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Via Olgettina 60, 20132, Milan, Italy.
Antonio CigliolaVita-Salute San Raffaele University, Via Olgettina 60, Milan, 20132, Italy.
Michela PiacentiniDepartment of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Via Olgettina 60, 20132, Milan, Italy.
Joseph M JacobDepartment of Urology, Upstate Medical University, Syracuse, NY, 13210, United States.
Gennady BratslavskyDepartment of Urology, Upstate Medical University, Syracuse, NY, 13210, United States.
Alina BasnetDivision of Hematology-Medical Oncology, Upstate Cancer Center, Syracuse, NY, 13210, United States.
Jeffrey S RossFoundation Medicine Inc, Cambridge, MA, 02141-2115, United States.
Andrea NecchiVita-Salute San Raffaele University, Via Olgettina 60, Milan, 20132, Italy.ORCID 0000-0002-3007-2756

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundthe homologous recombination deficiency signature (HRDsig) is emerging as a novel potential predictor of PARP-inhibitor (PARPi) response. We compared genomic alterations (GA) across BRCA2-loss, BRCA2 short variant-mutated (svmut), and BRCA2-wild type (wt) clinically advanced prostate carcinoma (CAPC) samples, combined with an assessment of HRDsig status to gain a better understanding of these biomarkers.

methodsComprehensive genomic profiling (CGP) was performed on 22 061 CAPC cases to evaluate all classes of GA. Microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic ancestry, were derived from sequencing data. HRDsig status was calculated using genome-wide copy number features. PD-L1 expression was assessed by IHC. Comparisons were performed using Fisher's exact test with Benjamini-Hochberg correction for false discovery.

resultsAmong 22 061 CAPC cases, 10.2% were HRDsig+. HRDsig+ and were enriched for BRCA2, RB1, MYC, RAD21, and AR alterations, while SPOP, MSI-high, high TMB, and MMR signatures were more frequent in HRDsig- cases. Across BRCA2-defined subgroups, 597 (2.7%) were BRCA2-loss, 1085 (4.9%) BRCA2-svmut, and 20 379 (92.4%) BRCA2-wt. Both BRCA2-loss and BRCA2-svmut were associated with higher GA burden and enrichment for RB1 alterations. BRCA2-loss cases displayed lower TMB-high incidence, while BRCA2-svmut showed higher MSI-high and TMB-high incidence. Most BRCA2 alterations were bi-allelic, with concurrent alterations in other HRR genes being rare.

conclusionsBRCA2-loss CAPC displays a distinct genomic landscape, marked by robust HRD features, suggesting the potential of higher sensitivity to PARPi. These findings highlight the relevance of HRDsig, and routinely use of CGP in refining patient selection for PARPi and guiding the design of future clinical trials.

Indexed as

Biomarkers, TumorHomologous RecombinationPrecision MedicineProstatic NeoplasmsAgedBRCA2 ProteinGenomicsHumansMaleMicrosatellite InstabilityMiddle AgedMutationBiomarkers, TumorBRCA2 ProteinBRCA2 protein, humanBRCAhomologous recombinationprecision medicineprostate cancer

Identifiers

PMID41871940
PMCPMC13253569

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Registered trials

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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.