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Androgen receptor mutations in prostate cancer
M Marcelli1, M Ittmann, S Mariani
1Department of Medicine, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas 77030, USA. marcelli@bcm.tmc.edu
Cancer Research
|March 8, 2000
Summary
Androgen receptor (AR) mutations are rare in early-stage prostate cancer but found in advanced metastatic disease, suggesting a role in disease progression.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Prostate cancer progression involves genetic alterations.
- The androgen receptor (AR) is crucial in prostate cancer development and treatment.
Purpose of the Study:
- To investigate the frequency and relevance of androgen receptor (AR) gene mutations in different stages of prostate cancer.
- To determine if AR mutations are associated with early-stage or metastatic prostate cancer.
Main Methods:
- Genomic DNA was extracted from 137 prostate cancer specimens (stage B and D1).
- PCR-single strand conformational polymorphism (SSCP) analysis of AR exons 2-8 and direct sequencing of exon 1 were performed.
- Progesterone receptor gene analysis was used as a control for genetic instability.
Main Results:
- No AR mutations were detected in 99 stage B prostate cancer specimens.
- Eleven AR mutations (8%) were identified in 8 of 38 stage D1 metastatic prostate cancer specimens.
- No mutations were found in the control progesterone receptor gene.
Conclusions:
- AR mutations are rare in early-stage prostate cancer and likely do not contribute to initial carcinogenesis.
- AR mutations are present in a subset of metastatic prostate cancer, suggesting a role in advanced disease progression or metastasis.