Determining the Impact of Spatial Heterogeneity on Genomic Prognostic Biomarkers for Localized Prostate Cancer.

DNA Genomics Humans Male Neoplasm Recurrence, Local / genetics Prognosis Prostatic Neoplasms / pathology
Biomarkers Genomics Heterogeneity Prognostication Prostate cancer

Journal

European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904

Informations de publication

Date de publication:
06 2022
Historique:
received: 17 02 2020
revised: 29 03 2020
accepted: 16 06 2020
pubmed: 2 7 2020
medline: 9 6 2022
entrez: 2 7 2020
Statut: ppublish

Résumé

Localized prostate tumors show remarkably diverse clinical courses, with some being cured by local therapy alone, while others rapidly relapse and have a lethal course despite precision surgery or radiotherapy. Many genomic biomarkers have been developed to predict this clinical behavior, but these are confounded by the extreme spatial heterogeneity of prostate tumors: most are multifocal and harbor multiple subclonal populations. To quantify the influence of spatial heterogeneity on genomic prognostic biomarkers, we developed a case-control high-risk cohort (n = 42) using a prospective registry, risk matched by clinicopathologic prognostic indices. Half of the cohort had early biochemical recurrence (BCR; ie, ≤18 mo), while half remained without evidence of disease for at least 48 mo after radical prostatectomy. We then genomically profiled multiple tumor foci per patient, analyzing 119 total specimens. These data allowed us to validate three published genomic prognostic biomarkers and quantify their sensitivity to tumor spatial heterogeneity. Remarkably, all three biomarkers robustly predicted early BCR, and all three were robust to spatiogenomic variability. These data suggest that DNA-based genomic biomarkers can overcome intratumoral heterogeneity: single biopsies may be sufficient to estimate the risk of early BCR after radical treatment in patients with high-risk disease. PATIENT SUMMARY: We investigated whether heterogeneity between tumor regions within the prostate affects the accuracy of DNA-based biomarkers predicting early relapse after prostatectomy. We observed persistent accuracy in predicting disease relapse, suggesting that spatial heterogeneity may not hinder biomarker performance.

Identifiants

DOI: 10.1016/j.euo.2020.06.005 PMID: 32605887
pubmed: 32605887
pii: S2588-9311(20)30083-3
doi: 10.1016/j.euo.2020.06.005
pii:
doi:

Substances chimiques

DNA 9007-49-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

362-365

Subventions

Organisme : CIHR
ID : 705649
Pays : Canada

Informations de copyright

Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Auteurs

Harry C Brastianos (HC)

Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada; Department of Radiation Oncology, Queen's University, Kingston, ON, Canada.

Jure Murgic (J)

Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.

Adriana Salcedo (A)

Ontario Institute for Cancer Research, Toronto, ON, Canada.

Melvin L K Chua (MLK)

Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Division of Radiation Oncology, National Cancer Centre Singapore, Singapore.

Alice Meng (A)

Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada.

Michael Fraser (M)

Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada.

Michael Brundage (M)

Department of Radiation Oncology, Queen's University, Kingston, ON, Canada.

Neil E Fleshner (NE)

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Theodorus van der Kwast (T)

Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.

Robert G Bristow (RG)

Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Manchester Cancer Research Center, Manchester, UK.

Paul C Boutros (PC)

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Human Genetics, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA; Broad Stem Cell Research Center, University of California, Los Angeles, CA, USA; Institute for Precision Health, University of California, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. Electronic address: PBoutros@mednet.ucla.edu.

Alejandro Berlin (A)

Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Techna Institute, University Health Network, Toronto, ON, Canada. Electronic address: alejandro.berlin@rmp.uhn.ca.

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Classifications MeSH

questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › Determining the Impact of Spatial...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Determining the Impact of Spatial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Determining the Impact of Spatial...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Récidive tumorale locale › Determining the Impact of Spatial...
questionsmedicales.fr › Diagnostic › Pronostic › Determining the Impact of Spatial...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Determining the Impact of Spatial...