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TP53 Gain-of-Function Mutations in Circulating Tumor DNA in Men With Metastatic Castration-Resistant Prostate Cancer.

Abstract：

BACKGROUND:Circulating tumor DNA (ctDNA), which can be assessed by liquid biopsy, can provide valuable genomic information that may affect treatment response in prostate cancer. The aim of this study was to characterize TP53 mutations and treatment history in prostate cancer. PATIENTS AND METHODS:This study included 143 patients with metastatic castration-resistant prostate cancer who had undergone ctDNA sequencing via Guardant360 testing. The presence or absence of TP53 mutations was analyzed along with treatment history for this group. TP53 mutations were further classified as gain of function (GOF) or not GOF, and analyzed with prior therapies. RESULTS:Chi-square analysis was performed for treatment history and TP53 status (further specified as all TP53 mutations or only TP53 GOF mutations). There were no associations between prior receipt of abiraterone/enzalutamide therapy and all TP53 mutations, or between docetaxel therapy and all TP53 mutations. However, TP53 GOF mutations had a positive association with prior abiraterone/enzalutamide therapy (P = .047). There was no association of TP53 GOF mutations with prior docetaxel therapy. The most frequent alterations co-occurring with all TP53 mutations were in AR, BRAF, EGFR, MYC, and PIK3CA. Common coalterations with TP53 GOF mutations included AR, BRAF, EGFR, RB1, NF1, and PIK3CA. There was an association of RB1 mutations with TP53 GOF mutations, versus RB1 mutations and no TP53 GOF mutations (P = .0036). CONCLUSION:TP53 GOF mutations may provide a valuable pathway to delineate metastatic castration-resistant prostate cancer TP53 mutations into therapeutic categories. Association with disease progression while receiving abiraterone/enzalutamide therapy was apparent in this study; however, further studies are needed to elaborate the therapeutic and prognostic implications.

journal_name

Clin Genitourin Cancer

journal_title

Clinical genitourinary cancer

authors

Chapman L,Ledet EM,Barata PC,Cotogno P,Manogue C,Moses M,Christensen BR,Steinwald P,Ranasinghe L,Layton JL,Lewis BE,Sartor O

doi

10.1016/j.clgc.2019.10.022

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

148-154

issue

eissn

1558-7673

issn

1938-0682

pii

S1558-7673(19)30326-X

journal_volume

pub_type

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TP53 Gain-of-Function Mutations in Circulating Tumor DNA in Men With Metastatic Castration-Resistant Prostate Cancer.