Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence  Xiaoyu Qu, Claudio Jeldres, Lena Glaskova, Cynthia Friedman, Sarah Schroeder, Peter S. Nelson, Christopher Porter, Min Fang  The Journal of Molecular Diagnostics  Volume 18, Issue 2, Pages 215-224 (March 2016) DOI: 10.1016/j.jmoldx.2015.10.001 Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 1 Representative fluorescent in situ hybridization (FISH) images. A–E: The four-color FISH detects rearrangements of TMPRSS2 and/or ERG: normal (A); typical fusion with the deletion of the interstitial region containing 3′-TMPRSS2 and 5′-ERG (B); rearrangement of 5′-TMPRSS2 (C); rearrangement of 3′-ERG (D); and complex fusion revealing the simultaneous presence of the fusion signal and signals representing additional rearrangements (E). An illustration of the signal pattern is inserted at the bottom left corner of each image. F and G: AR FISH: normal AR signal pattern with one copy each of the AR (orange) and X-chromosome centromere (CEPX, green) signal per nucleus (F), and AR gain detected in the current study revealing concurrent gain of AR and CEPX (G). H–K: PTEN FISH: normal PTEN signal pattern revealing two signals each for the centromere of chromosome 10 (CEP10, green) and the PTEN gene (orange) per nucleus (H); trisomy 10 revealing three copies each of the CEP10 and the PTEN signals (I); heterozygous PTEN deletion indicated by the presence of two CEP10 signals but only one copy of the PTEN signal (J); and homozygous PTEN deletion demonstrated by the presence of two CEP10 signals but none of the PTEN signal (K). White and orange arrows highlight normal and abnormal cells, respectively. The Journal of Molecular Diagnostics 2016 18, 215-224DOI: (10.1016/j.jmoldx.2015.10.001) Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 2 Prevalence of aberrations detected by the fluorescent in situ hybridization (FISH) panel and Kaplan-Meier curves of biochemical recurrence (BcR)–free survival in patients grouped based on FISH findings. A, C, E, and G: The prevalence of different FISH abnormalities detected by TMPRSS2/ERG, PTEN/CEP10, AR/CEPX, and the three-marker panel, respectively. B, D, F, and H: The Kaplan-Meier BcR-free survival in patients grouped based on FISH findings. All curves are marked at censoring times. Normal is denoted by white in all pie charts and by black lines in all Kaplan-Meier curves. A and B: Solid red, dashed red, solid blue, dashed blue, and gray denote typical fusion, atypical or complex fusion, alternative rearrangement, rearranged 3′-ERG without fusion with TMPRSS2, and copy number increase (CNI), respectively. C and D: Red and blue denote PTEN deletion and trisomy 10, respectively. E and F: Red denotes AR gain. G and H: Blue, red, green, dashed red, and gray denote patients with TMPRSS2:ERG fusion only, PTEN deletion only, AR gain plus trisomy 10, PTEN deletion plus ERG rearrangement (including TMPRSS2:ERG fusion), and other combinatorial abnormalities, respectively. Log-rank P values in D and H were calculated between the patients with abnormal and normal results. The Journal of Molecular Diagnostics 2016 18, 215-224DOI: (10.1016/j.jmoldx.2015.10.001) Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 3 Kaplan-Meier curves of biochemical recurrence–free survival in patients with different tumor stages grouped based on fluorescent in situ hybridization. All curves are marked at censoring times. A and C: Patients with prostate cancer T2 at the time of surgery. B and D: Patients with prostate cancer T3/4. The Journal of Molecular Diagnostics 2016 18, 215-224DOI: (10.1016/j.jmoldx.2015.10.001) Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions