4904 - Molecular characterization of metastatic urothelial carcinoma (mUC) in prior or current smokers (PCS) vs non-smokers (NS)

Background

Even though smoking is one of the most recognized risk factors, NS also develop mUC. Identifying molecular drivers of disease progression in NS have the potential to provide novel targets for drug development. We hypothesized that there will be a difference in genomic profile of mUC in NS vs PCS.

Methods

Tumour tissue undergoing comprehensive genomic profiling (CGP) from patients with mUC were included from NS and age matched PCS within the same time period (2014-19). Clinical and CGP data were retrospectively collected. CGP was performed using FoundationOne (Foundation Medicine, Cambridge, MA), which provides exonic coverage of 315 genes.

Results

See table.Table:

943P

Conclusions

While the overall number of genomic alteration per patient and alteration frequencies were similar in NS vs PCS, we found a significantly higher frequency of MLL2 alterations in NS (p < 0.05). This finding is in agreement with previous reports of MLL2 alterations in UC; however, its significantly higher prevalence in NS is a novel finding and may suggest different oncogenic pathways in NS. It’s interesting to note that MLL2 alterations have been reported as drivers of self-renewal in bladder cancer stem cells (Yang et al, Euro Urol 2017, PMID 27387124).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Huntsman Cancer Institute.

Funding

Has not received any funding.

Disclosure

B.L. Maughan: Advisory / Consultancy: Peloton Therapeutics; Advisory / Consultancy: BMS; Advisory / Consultancy: Tempus; Advisory / Consultancy: Bayer; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Janssen Oncology; Advisory / Consultancy: Astellas Pharma. N. Agarwal: Advisory / Consultancy: Astellas; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Argos; Honoraria (institution), Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: Exelixis; Honoraria (institution), Advisory / Consultancy: Eisai; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Foundation One; Honoraria (institution), Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (institution), Advisory / Consultancy: Medivation; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Nektar; Honoraria (institution), Advisory / Consultancy: Genentech; Honoraria (institution), Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Pharmacyclics; Honoraria (institution): Sanofi. All other authors have declared no conflicts of interest.