Germline Mutations and Polymorphisms of Androgen Receptor in Prostate Cancer Patients: Frequency and Results of in Silico Analysis

Document Type: Research Articles


1 Department of Biomedical Science, Division of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.

2 Medical Genetics Working Group, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.

3 Graduate School Biomedical Sciences Master Program, Faculty of Medicine, Universitas Padjajaran, Bandung, Indonesia.

4 Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia.

5 Faculty of Medicine, Brawijaya University, Malang, Indonesia.

6 Departement of Urology, Faculty of Medicine, Muhammadiyah University, Surakarta, Indonesia.


Background: Germline and somatic polymorphisms and mutations of the Androgen Receptor (AR) gene are known to
be associated with the incidence of prostate cancer (PCa) in different populations. In this study we assessed germline AR
polymorphisms and mutations in PCa patients with prediction of pathogenicity of the identified mutations by in silico
analysis. Methods: Diagnosis of PCa was based on histopathology of prostate tissue (Gleason Score criteria) and serum
prostate-specific antigen (PSA) levels. Genomic DNA was extracted from peripheral blood of 38 patients. All exons and
exon-intron boundaries of AR were amplified using polymerase chain reactions (PCR) followed by Sanger sequencing.
In silico analysis was performed using Polyphen-2 and Mutation Taster®. Results: Two polymorphisms, CAG repeat
sequence (13-34 repeats in length) and p.Pro214Glu (MAF: 0.0789) located in exon 1 were identified. A missense
mutation (c.47C>A/p.Pro146Glu) and in-frame deletion of a CAG sequence leading to loss of Arginine at codon 85
(c.252_254delCAG/p.Arg85-) were identified in a 70 year old patient with a Gleason Score and PSA level of 2 and
2.4ng/dL, respectively. His PSA level decreased to < 0.5 ng/dL after 9 months of androgen deprivation therapy. Identified
mutations were predicted to be non-disease causing by Polyphen-2 and Mutation Taster®. Conclusion: Our data
demonstrated that the frequency of germline mutations of AR was low in PCa patients in Indonesia (5.26%: 2/38 alleles),
so that they are not likely to be major etiological factors. The in silico analysis of identified AR mutations in this study
corroborated the clinopathology features of the patient.


Main Subjects