PO-308 Identification of genomic patterns predictive of upgrading in low-grade prostate cancer

Introduction Active surveillance (AS) for men with low-risk prostate cancer (PCa) currently depends on repeated biopsies for prognostication. We aim to identify molecular patterns that are present in initial PCa biopsies that inform future histopathological upgrading of PCa for men on AS. Material and methods TAPS2.0 and Patchwork were respectively used to establish somatic copy number aberrations (SCNAs) for 44 Gleason score (GS)6 (3+3) TCGA PRAD Affymetrix SNP6.0 and 18 GS6 (3+3) ICGC WGS samples. Elastic net regularisation was used to identify SCNA predictors of biochemical recurrence (BCR). In an internal cohort, SCNAs were established using QDNAseq from initial and repeat biopsies of 5 men on AS, using low-pass WGS. Four of the 5 men upgraded from a GS6 to GS7 (3+4) upon repeat biopsy whilst one remained GS6. Results and discussions SCNAs were robustly established for 62 GS6 TCGA and ICGC PCas. The most frequent copy number losses were at 8 p (50%), 13q (29%) and 6q (26%). Applying a Shannon-diversity index on SCNAs provided a measure of genomic heterogeneity and indicated a trend towards increased diversity in PCa of men with BCR (p-value=0.087, t-test). Six cytobands with recurrent SCNAs were identified as predictive of BCR, including a loss on 10q11 and a gain on 2 p13. These predictive SCNAs were interrogated in genomes from our internal cohort of initial and repeat biopsies. Copy number losses were identified at 8 p (46%), 13q (23%), and 6q (46%), and were comparable in frequency to losses in TCGA and ICGC. None of the six predictors were detected in the initial PCa biopsy of the stable patient, while two predictors were found in men who had upgraded to GS7: 14q13 (gain), present in two men, and 6q11 (loss), in another man. Patients that upgraded had the highest similarities (81%) of SCNAs between patient-matched initial and repeat biopsies. Given that these biopsies were taken furthest apart in the prostate gland, missampling and GS is likely not to affect prediction. Conclusion SCNAs indicative of upgrading were identified in GS6 TCGA-ICGC data using BCR as a surrogate for histopathological upgrading whilst on AS. These were observed to some extent in an internal cohort of men on AS. Validation of these predictors in men on AS is currently on-going in a further 8 men and may provide the basis for developing a prognostication tool to guide therapy for men with early prostate cancer.