Aarhus, Denmark (UroToday.com) Dr. John Sfakianos from the Icahn School of Medicine at Mount Sinai in New York presented a novel mouse model of muscle-invasive bladder cancer that was capable of orthotopic transplantation. This was achieved using OHBBN-induced carcinogenesis in mice, with global GFP and luciferase expression Tg(CAG-luc-eGFP). Sorting GFP+ tumor implants to the muscle wall of naïve FVB/NJ mice allowed for the identification of distinct tumor cells from host cells.
Lineage populations were identified using surface antigens and single cell and bulk RNA sequencing analyses were used to assess the expression of multiple clinical subtypes in a single primary OHBBN bladder tumor. Dr. Sfakianos therefore illustrated that conventional gene expression “consensus classifiers” fail to fully consider the intratumoral molecular heterogeneity that exists within these tumors, and may falsely assume that there is a “predominant signature” when in fact multiple subtypes exist within the tumor. Limitations of single cell sequencing were noted to include the loss of data granularity during analysis, as well as the fact that a murine model does may not fully encompass the true behavior of human bladder tumors.
Abstract take-home message:
- Consensus classifiers and molecular subtyping may oversimplify the molecular heterogeneity that exists within bladder tumors, as identified in single cell sequencing analyses performed on an OHBBN bladder tumor murine model
Presented by: John Sfakianos, MD, Assistant Professor of Urology and Urologic Oncology at the Icahn School of Medicine at Mount Sinai, New York