PTEN Genomic Deletions Is an Early Event Associated with ERG Gene Rearrangements in Prostate Cancer
TA Bismar, M Yoshimoto, RT Vollmer, Q Duan, M Firszt, J Corcos, JA Squire. University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada; Queen's University, Kingston, ON, Canada; VA and Duke University Medical Centers, Durham, NC; McGill University, Montreal, QC, Canada
Background: ERG gene rearrangements and PTEN genomic deletions are two of the most common genetic alteration in prostate cancer (PCA). The interaction and significance of those two genetic aberrations in relation to disease development and progression is still controversial.
Design: We interrogated initial cohort of 220 men with localized PCA using fluorescence in-situ hybridization for ERG rearrangements and PTEN genomic deletions.
Results: ERG rearrangements and PTEN deletions incidence in PCA was significantly higher than in HGPIN and benign prostate tissue (p< 0.0001). ERG rearrangements and PTEN deletions were detected in 41.9% and 42.6% of patients' tumors, 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=0.0001). Furthermore, in 29 cases where all three tissues were available, PTEN genomic aberration levels showed significant difference between PCA vs. benign (p=0.005) and HGPIN (p=0.02) reflective of accumulating genomic aberrations at early stages of disease progression. Within this cohort, 71.4% of homozygous and 44.2% of hemizygous PTEN deletions occurred simultaneously with ERG rearrangements. Stratified based on 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) compared to moderately and well-differentiated tumors (GS 6 & 7).
Conclusions: Our data confirm significant association between ERG gene rearrangement and PTEN genomic aberrations in PCA. Furthermore, our analysis provides further support for the observation that homozygous PTEN deletions can occur within subset of HGPIN lesions, and show accumulating genetic aberrations with disease progression, evidenced by higher detection in PCA vs. HGPIN and increased PTEN homozygous deletions in Gleason scores 8-10 vs. 6-7.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 125, Wednesday Afternoon