PTEN genomic deletion is an early event associated with ERG gene rearrangements in prostate cancer
Article first published online: 29 JUN 2010
© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL
Volume 107, Issue 3, pages 477–485, February 2011
How to Cite
Bismar, T. A., Yoshimoto, M., Vollmer, R. T., Duan, Q., Firszt, M., Corcos, J. and Squire, J. A. (2011), PTEN genomic deletion is an early event associated with ERG gene rearrangements in prostate cancer. BJU International, 107: 477–485. doi: 10.1111/j.1464-410X.2010.09470.x
- Issue published online: 25 JAN 2011
- Article first published online: 29 JUN 2010
- Accepted for publication 18 February 2010
- ERG rearrangements;
- fluorescence in-situ hybridization;
- high-grade prostatic intra-epithelial neoplasia;
- prostate cancer;
- Gleason score;
- disease progression
What’s known on the subject? and What does the study add?
So far we know that ERG rearrangements and PTEN deletions interact to induce prostate cancer in transgenic mice. The study confirms that an association also exists between the two genetic aberrations in human prostate cancer, as there is increased incidence of PTEN deletions in cases with ERG rearrangements.
To investigate the interaction between, and significance of, ERG gene rearrangements and PTEN genomic deletions in relation to the development and progression of prostate cancer (PCA).
PATIENTS AND METHODS
We interrogated an initial cohort of 220 men with localized PCA using fluorescence in situ hybridization for ERG rearrangements and PTEN genomic deletions.
The incidences of ERG rearrangements and PTEN deletions in PCA were significantly higher than in high-grade prostatic intra-epithelial neoplasia (HGPIN) and benign prostate tissue (P < 0.001). ERG rearrangements and PTEN deletions were detected in 41.9 and 42.6% of patients’ tumours, respectively. ERG rearrangements were never detected in benign prostate tissue, while PTEN aberrations were present at a basal level of 4.6%. PTEN hemizygous deletions showed higher frequency than homozygous deletions within each diagnostic category from benign prostate tissue to HGPIN and PCA (P ≤ 0.001). Furthermore, in 29 patients where all three tissues were available, PTEN genomic aberrations in PCA were significantly different from those in benign tissue (P = 0.005) and HGPIN (P = 0.02), reflecting the accumulation of genomic aberrations in the early stages of disease progression. Within this cohort, 71.4% of homozygous and 44.2% of hemizygous PTEN deletions occurred simultaneously with ERG rearrangements (P ≈ 0). Stratified according to Gleason score (GS), hemizygous PTEN deletions across various GS groups were observed at a higher frequency than homozygous deletions. However, PTEN homozygous deletions showed positive trends with higher GS, increasing in poorly differentiated PCA (GS 8–10) in comparison to moderately and well differentiated tumours (GS 6 and 7).
We show significant association between ERG gene rearrangements and PTEN genomic aberrations in subset of PCA. Our analysis also provides further support for the observation that homozygous PTEN deletions can occur within the subset of HGPIN lesions, and shows accumulating genetic aberrations with disease progression, evidenced by higher detection in PCA than in HGPIN and more PTEN homozygous deletions in GS 8–10 than in 6–7.