Clinical and Genomic Factors Associated with Greater Tumor Mutational Burden in Prostate Cancer

Helen Y. Hougen; Ryon P. Graf; Gerald Li; Julia C.F. Quintanilha; Douglas I. Lin; Jeffrey S. Ross; Sanoj Punnen; Brandon A. Mahal

doi:10.1016/j.euros.2023.08.001

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Clinical and Genomic Factors Associated with Greater Tumor Mutational Burden in Prostate Cancer

Journal article

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Clinical and Genomic Factors Associated with Greater Tumor Mutational Burden in Prostate Cancer

Helen Y. Hougen, Ryon P. Graf, Gerald Li, Julia C.F. Quintanilha, Douglas I. Lin, Jeffrey S. Ross, Sanoj Punnen and Brandon A. Mahal

European urology open science (Online), Vol.55, pp.45-49

09/01/2023

DOI: 10.1016/j.euros.2023.08.001

PMCID: PMC10470357

PMID: 37662703

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Abstract

Tumor mutational burden (TMB) is a biomarker that predicts response to immune checkpoint inhibitor therapy. We currently lack a comprehensive understanding of how genomic and clinical factors correlate with TMB. We used a clinicogenomic database to assess independent predictors of TMB levels. The study included 2740 prostate cancer specimens from prostate gland (51.6%), lymph nodes (14.6%), and bone (10.4%). Androgen deprivation therapy use beyond 24 mo was weakly associated with high TMB (fold-change estimate [FCE] 1.14, 95% confidence interval [CI] 1.03–1.26; p = 0.009). In comparison to the prostate gland, metastases in the bladder (FCE 1.20, 95% CI 1.02–1.42; p = 0.029), liver (FCE 1.26, 95% CI 1.10–1.43; p < 0.001), and other locations (FCE 1.26, 95% CI 1.11–1.43; p < 0.001) were associated with high TMB. Microsatellite instability high (FCE 8.46, 95% CI 6.42–11.15; p < 0.001) and intermediate (FCE 1.77, 95% CI 1.46–2.14; p < 0.001) status were associated with greater TMB. Altered genes associated with greater TMB included MLH1 (FCE 1.81; p = 0.004), MSH2 (FCE 1.87; p < 0.001), MSH6 (FCE 1.92; p < 0.001), BRCA2 (FCE 1.69; p < 0.001), CDK12 (FCE 1.40; p < 0.001), MRE11 (FCE 2.28; p = 0.016), and PALB2 (FCE 2.08; p < 0.001). Our study demonstrates that TMB is relatively stable over lines of therapies and can be used to guide treatment at diagnosis or in later lines for patients with metastatic prostate cancer. The number of genetic mutations in a tumor (tumor mutational burden, TMB) may help in predicting a patient’s response to immunotherapy in advanced prostate cancer. We evaluated clinical and genetic factors that may affect TMB. We found that metastases in the bladder and liver are more likely to have high TMB than the primary tumor. Some individual genes are associated with high TMB. No prior treatment type was strongly associated with TMB, suggesting that TMB can be used to guide treatment at any time point. These data were presented at the American Society of Clinical Oncology 2023 Genitourinary Cancers Symposium.

Biomarkers

Genomics

Microsatellite instability

Prostatic neoplasms

Details

Title: Subtitle: Clinical and Genomic Factors Associated with Greater Tumor Mutational Burden in Prostate Cancer
Creators: Helen Y. Hougen - University of Miami
Ryon P. Graf - Foundation Medicine, Inc., Cambridge, MA, USA
Gerald Li - Foundation Medicine, Inc., Cambridge, MA, USA
Julia C.F. Quintanilha - Foundation Medicine, Inc., Cambridge, MA, USA
Douglas I. Lin - Foundation Medicine, Inc., Cambridge, MA, USA
Jeffrey S. Ross - SUNY Upstate Medical University
Sanoj Punnen - Sylvester Comprehensive Cancer Center
Brandon A. Mahal - University of Miami
Resource Type: Journal article
Publication Details: European urology open science (Online), Vol.55, pp.45-49
Publisher: Elsevier B.V
DOI: 10.1016/j.euros.2023.08.001
PMID: 37662703
PMCID: PMC10470357
ISSN: 2666-1683
eISSN: 2666-1683
Number of pages: 5
Language: English
Date published: 09/01/2023
Academic Unit: Urology
Record Identifier: 9984701542502771

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