Clinical utility of androgen receptor gene aberrations in circulating cell-free DNA as a biomarker for treatment of castration-resistant prostate cancer.

Clinical utility of androgen receptor gene aberrations in circulating cell-free DNA as a biomarker for treatment of castration-resistant prostate cancer.

Publication date: Mar 11, 2019

The therapeutic landscape of castration-resistant prostate cancer (CRPC) has rapidly expanded. There is a need to develop noninvasive biomarkers to guide treatment. We established a highly sensitive method for analyzing androgen receptor gene (AR) copy numbers (CN) and mutations in plasma circulating cell-free DNA (cfDNA) and evaluated the AR statuses of patients with CRPC. AR amplification was detectable in VCaP cell line (AR amplified) genomic DNA (gDNA) diluted to 1.0% by digital PCR (dPCR). AR mutation were detectable in LNCaP cell line (AR T878A mutated) gDNA diluted to 0.1% and 1.0% by dPCR and target sequencing, respectively. Next, we analyzed AR status in cfDNA from 102 patients. AR amplification and mutations were detected in 47 and 25 patients, respectively. As a biomarker, AR aberrations in pretreatment cfDNA were associated with poor response to abiraterone, but not enzalutamide. In serial cfDNA analysis from 41 patients, most AR aberrations at baseline diminished with effective treatments, whereas in some patients with disease progression, AR amplification or mutations emerged. The analysis of AR in cfDNA is feasible and informative procedure for treating patients with CRPC. cfDNA may become a useful biomarker for precision medicine in CRPC.

Open Access PDF

Sumiyoshi, T., Mizuno, K., Yamasaki, T., Miyazaki, Y., Makino, Y., Okasho, K., Li, X., Utsunomiya, N., Goto, T., Kobayashi, T., Terada, N., Inoue, T., Kamba, T., Fujimoto, A., Ogawa, O., and Akamatsu, S. Clinical utility of androgen receptor gene aberrations in circulating cell-free DNA as a biomarker for treatment of castration-resistant prostate cancer. 04201. 2019 Sci Rep (9):1.

Concepts Keywords
Aberrations LNCaP
Abiraterone CRPC
Androgen Receptor Enzalutamide
Biomarker Circulating free DNA
Biomarkers Pyridines
Castration Nonsteroidal antiandrogens
Enzalutamide DNA
GDNA Biomarkers
Mutation Prostate cancer
Plasma Chemistry
Prostate Chemical compounds
Prostate Cancer Branches of biology
Sci
Sequencing

Semantics

Type Source Name
disease MESH diagnosis
disease MESH Metastasis
gene UNIPROT YES1
gene UNIPROT CTBP1
gene UNIPROT DYRK3
gene UNIPROT IK
gene UNIPROT ABRA
drug DRUGBANK Bicalutamide
disease MESH estrogens
gene UNIPROT ADHFE1
gene UNIPROT DEPP1
gene UNIPROT GOPC
gene UNIPROT BTG3
disease MESH tumor
gene UNIPROT LARGE1
gene UNIPROT EHD1
disease MESH development
disease MESH multiple
drug DRUGBANK Cabazitaxel
drug DRUGBANK Docetaxel
gene UNIPROT FLVCR1
drug DRUGBANK Pidolic Acid
disease DOID PCa
gene UNIPROT TGM1
gene UNIPROT XIRP1
drug DRUGBANK Coenzyme M
disease MESH disease progression
drug DRUGBANK Enzalutamide
drug DRUGBANK Abiraterone
pathway BSID Prostate cancer
disease DOID prostate cancer
disease MESH prostate cancer

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *