DNA copy number alterations in bladder urothelial carcinoma: concordance between biopsy samples and cancer stem-like cells

Bladder cancer (BC) is the seventh most common cancer worldwide. Over 90 % are transitional cell carcinoma (TCC) and at least 70 % of TCC are superficial with unpredictable clinical outcome. It has been suggested that the heterogeneity of BC originates from underlying genetic alterations that lead to different pathways of tumor development and progression. In the last decade a subset of neoplastic cells, known as cancer stem cells (CSCs) has been isolated and characterized from different kind of tumors, including BC. Since the CSC subpopulation seems to be the driving force for tumor initiation, growth and relapse, the identification of a specific CSC genomic signature is a crucial step in order to find new markers for tumor recurrence and progression and new targeted therapies. In this study we compare the genomic profiles of whole biopsies of 16 TCCs with the corresponding CSCs isolated from them, in order to identify any shared copy number alterations (CNAs). The molecular karyotype was evaluated by means of Human Genome kit 8×60 K (Agilent Technologies). The comparison between the genomic profiles evidenced 5 CNAs shared by at least three samples: 3p, two at 9p, 9q and 19q. In particular we observed the loss of tumor suppressor genes (CDKN2A, CDKN2B, PTPRD, TSC1, PTCH1, ABL1 and NOTCH1) while the gain of PPARG, a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. Gene Ontology analysis showed that the most represented classes in the CNAs of biopsies and CSCs are apoptosis and transcription regulation. The identification of a specific genomic signature that characterize CSCs is an outstanding endpoint and the identification of commonly shared alterations could provide a first clue in deciphering putative genomic markers useful for diagnostic, prognostic or therapeutic purpose