PO-326 Genetic stability of multiple recurrences in bladder cancer patients

Introduction To describe the origin and the genetic relationship between primary bladder tumours and their recurrences, different models were proposed, such as, field cancerization, seeding, and intraepithelial migration. This study aims to investigate the genetic relationship in syn- and metachronous bladder tumours using different types of data, and to evaluate the proposed models. Material and methods The exophytic part of primary and recurrent urothelial tumours were collected by cold-cup biopsies from patients undergoing transurethral resection at the Lund University Hospital, Sweden, between 2001 and 2007. In total, 51 tumours from 19 patients and their 19 matched peripheral blood samples were collected and hybridised on Illumina HumanCNV370-Duo Genotyping array. Copy number data was extracted from GenomeStudio 2 software, and normalised using transformed quantile normalisation (tQN). Mirrored B allele frequency values were segmented using BAFsegmentation. Mutation calling was performed using targeted cancer gene sequencing panel. Gene expression data was generated using Illumina HumanHT-12 expression array. Results and discussions A manual inspection of all copy number alterations (CNAs) profiles was performed. Normal cells content, tumour ploidy, and sub clonality were calculated, and the relationship between the primary and recurrent tumours were estimated. Preliminary results show that CNAs are early and stable events during the tumour evolution. Part of the syn- and metachronous bladder tumours shared similar mutational and CNAs profiles. However, even with similar profiles, some events such as loss of heterozygosity in the primary tumours, were not observed in the recurrent tumours, constituting incompatible events. Samples with mutations in TP53 or amplification in MDM2 showed higher number of break points in the genome. A further analysis will be performed using the available CNAs, expression, and mutational data. Conclusion The genetic relationship in syn- and metachronous bladder tumours was investigated using different data types providing a better understanding of bladder cancer evolution. The presence of similar mutational and CNAs profiles combined with incompatible events suggests that the primary and the recurrent tumours were generated separately from a common ancestor. These findings highlight a tumour evolution scenario of a clonal cancerized field.