Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2024

Aims: MTAP deletion is an emerging target for MAT2A and PRMT5 inhibitors. We aim to describe the prevalence and other characteristics of MTAP deletions in the OMICO CaSP/MoST population.

Methods: MoST and CaSP are screening programs enrolling patients with advanced cancers for molecular sequencing. MTAP deletion was assessed directly by Foundation Medicine & Avenio (FMI&A) and indirectly by TSO500 via analysis of background reads adjacent to CDKN2A. We report prevalence across both platforms , cancer primary site and co-mutations.  Kaplan-Meier survival analysis was performed to assess prognostic value of MTAP. 

Results: 686/8,926 (7.7%) were found to have MTAP deletions. 497/3,698 (13.4%) were identified using FMI&A, 189/5,238 (3.6%) using the TSO500. Table 1 shows most common tumours with MTAP deletions. Deletions were rare in Colorectal (1%), Gynaecological (3%) and Prostate Cancers (0.8%). MTAP deletion was associated with significantly worse median survival in pancreas cancer (9.1 vs 13m; HR 0.60 [95% CI 0.52-0.69];P<0.001) but there were no statistically differences detected in survival for other cancers. In the FMI&A datasets 86% of pts had codeletion of CDKN2A. TP53, KRAS andEGFR co-alterations were the next most common. Activating co-alterations in EGFR, KRAS & ALK were frequently seen in lung cancers.

Conclusions: MTAP deletions are common in the MoST/CaSP population, most frequently in CNS, pancreas, lung and melanoma patients.  Detection of MTAP deletion was higher with the FM1&A paltform. MTAP deletions co-existed with CDKN2A deletions in >80% of the cohort. Other targetable mutations were also found to co-occur. MTAP deletions may be associated with worse survival in pancreatic cancer.