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. 2020 Oct;80(14):1253-1262.
doi: 10.1002/pros.24057. Epub 2020 Aug 17.

Feasibility and performance of a novel probe panel to detect somatic DNA copy number alterations in clinical specimens for predicting prostate cancer progression

Wennuan Liu  1   2 , Jun Hou  1 , Jacqueline Petkewicz  3 , Rong Na  1 , Chi-Hsiung Wang  1   2 , Jishan Sun  1   2 , Johnie Gallagher  1 , Yedida Y Bogachkov  1 , Laura Swenson  1 , MaryAnn Regner  4 , W Kyle Resurreccion  1 , William B Isaacs  5 , Charles B Brendler  1   2 , Susan Crawford  1   2 , S Lilly Zheng  1   2 , Brian T Helfand  1   2   3 , Jianfeng Xu  1   2
Affiliations

Feasibility and performance of a novel probe panel to detect somatic DNA copy number alterations in clinical specimens for predicting prostate cancer progression

Wennuan Liu et al. Prostate. 2020 Oct.

Abstract

Background: To assess the feasibility of a novel DNA-based probe panel to detect copy number alterations (CNAs) in prostate tumor DNA and its performance for predicting clinical progression.

Methods: A probe panel was developed and optimized to measure CNAs in trace amounts of tumor DNA (2 ng) isolated from formalin-fixed paraffin-embedded tissues. Ten genes previously associated with aggressive disease were targeted. The panel's feasibility and performance were assessed in 175 prostate cancer (PCa) patients who underwent radical prostatectomy with a median 10-year follow-up, including 42 men who developed disease progression (either metastasis and/or PCa-specific death). Association with disease progression was tested using univariable and multivariable analyses.

Results: The probe panel detected CNAs in all 10 genes in tumor DNA isolated from either diagnostic biopsies or surgical specimens. A four-gene model (PTEN/MYC/BRCA2/CDKN1B) had the strongest association with disease progression; 64.3% of progressors and 22.5% of non-progressors had at least one CNA in these four genes, odds ratio (OR) (95% confidence interval) = 6.21 (2.77-13.87), P = 8.48E-06. The association with disease progression remained significant after adjusting for known clinicopathological variables. Among the seven progressors of the 65 patients with clinically low-risk disease, three (42.9%) had at least one CNA in these four genes.

Conclusions: The probe panel can detect CNAs in trace amounts of tumor DNA from biopsies or surgical tissues at the time of diagnosis or surgery. CNAs independently predict metastatic/lethal cancer, particularly among men with clinically low-risk disease at diagnosis. If validated, this may improve current abilities to assess tumor aggressiveness.

Keywords: probe panel; prostate cancer progression; somatic CNA.

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References

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