943PMolecular characterization of metastatic urothelial carcinoma (mUC) in prior or current smokers (PCS) vs non-smokers (NS)

• Published in: Annals of oncology Vol. 30; no. Supplement_5
• Main Authors: Sacristan Santos, V, Esther, J, Maughan, B L, Wesolowski, S, Lin, E, Hahn, A, Sirohi, D, Rathi, N, Swami, U, Nussenzveig, R, Agarwal, N
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.10.2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz249.040

Abstract 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:943PNon-smokerSmokerP valueMedian age at diagnosis, years (range)66.5 (33-86)67 (35-85)0.94Site of primary0.009Bladder37 (80%)39 (100%)Upper tract9 (19.6%)0Urethral1 (<1%)0Gender0.001Male3238Female141Median number of genomic alterations (range)7 (1-17)7 (1-18)0.26MLL2 gene alteration1110.01 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). 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.