Abstract 5053: Targeted sequencing panel for comprehensive MTAP deletion detection in diverse cancer types

Objective: Methylthioadenosine phosphorylase (MTAP) deletion is a prevalent genomic alteration across various malignancies, often correlated with unfavorable clinical outcomes. The detection of MTAP deletions offers opportunities for personalized therapeutic strategies aimed at exploiting specific metabolic vulnerabilities. However, existing detection methodologies are frequently costly and labor-intensive, highlighting the necessity for an efficient and economical detection panel. Developing such a tool is essential for the timely identification of MTAP deletions, facilitating prompt initiation of targeted therapies and improving patient prognoses. Methods: We retrospectively analyzed 5,787 tissue samples from patients diagnosed with 11 distinct cancer types, including colorectal, lung, liver, gastric, bladder, pancreatic, and esophageal cancers. A targeted sequencing approach (approximately 1,000X coverage) was employed using the GeneseeqPrime™ panel, which encompasses 437 cancer-related genes. Additionally, an independent cohort of 29 cancer samples was analyzed to assess the concordance of our sequencing panel with Fluorescence In Situ Hybridization (FISH) and Immunohistochemistry (IHC). Results: The evaluation of MTAP deletions across a spectrum of cancer types revealed significant variations in both total and homozygous deletion rates. Bladder cancer exhibited a total deletion rate of 43.43%, with homozygous deletions accounting for 11.11%. Esophageal squamous cell carcinoma indicated a total deletion rate of 46.15%, with homozygous deletions at 15.73%. Glioblastomas displayed the highest prevalence of total deletions at 58.33%, including 30.21% homozygous deletions. Furthermore, non-small cell lung cancer (NSCLC) and pancreatic cancer had total deletion rates of 35.84% and 42.55%, respectively, with homozygous deletions at approximately 8.21% and 15.55%. Our panel demonstrated perfect concordance with both FISH and IHC (100% agreement). Conclusion: This study establishes the variable prevalence of MTAP deletions across multiple cancer types, underscoring its significance as a prognostic biomarker associated with poor outcomes. The GeneseeqPrime™ panel provides a rapid and cost-effective means for identifying MTAP deletions, facilitating timely diagnosis and personalized therapeutic strategies. Further validation in larger cohorts and clinical settings is warranted to enhance its applicability in routine oncological practice. Citation Format: Hua Bao, Haimeng Tang, Rui Liu, Ningyou Li, Min Wu, Xunbiao Liu, Zhili Chang, Xue Wu. Targeted sequencing panel for comprehensive MTAP deletion detection in diverse cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5053.