Abstract 1775: The profiling of MTAP homozygous deletion (MTAPhd) in a Chinese pan-cancer cohort

Abstract

Abstract Background: Protein arginine methyltransferase 5 (PRMT5) is an enzyme that catalyzes the transfer of methyl groups from S-adenosylmethionine (SAM) to the arginine residues on histones and other proteins. The dysregulation of this methylation is critical in the development of certain cancers. MTAPhd can cause anti-tumor effect of PRMT5 inhibitor via a synthetic lethality mechanism. Methods: 9,202 cases were collected and subjected to NGS for genomic alteration detection. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China. The hybrid capture panel covered 450 genes, heterozygous snps were used for MTAPhd identification, the detection rate of MTAPhd was measured and fisher’s exact test was used for analyzing the correlation with age, stage, subtype and gender. Results: In total, 6.8% (626/9202) cases had MTAPhd. In 626 dataset, 220 was female and 406 was male. Age was from 3 to 91 with median 63. 25, 43, 74 and 119 was in clinical stage I, II, III, IV, respectively. Patients with age < 60 had lower odds (OR 0.60; 95% CI 0.51-0.71; p < 0.001) of occurring MTAPhd compared to age >= 60. Clinical stage I and II had lower odds (OR 0.59; 95% CI 0.44-0.79; p < 0.001) compared to stage III and IV. Adenocarcinoma had lower odds (OR 0.17; 95% CI 0.14-0.21; p < 0.001) compared to squamous carcinoma. Female had lower odds (OR 0.70; 95% CI 0.59-0.83; p < 0.001). MTAPhd occurred in multiple cancers, among which it was more likely to occur in esophageal carcinoma (72/298; 24.2%), brain tumor (14/66; 21.2%) and bladder urothelial carcinoma (67/348, 19.3%). The detection rates of the top three cancer types in the sample size were lung cancer (208/2743, 7.6%), pancreatic cancer (48/794, 6.0%) and colorectal carcinoma (7/756, 0.9%), respectively. Lung squamous cell carcinoma (LUSC) (13.5% vs 19.3%, p = 0.008) and bladder urothelial carcinoma (BLCA) (19.3% vs 25.5%, p = 0.045) of Chinese cohort had lower rate of MTAPhd compared to TCGA cohort. 53 out of 626 had no driver mutations associated with recommended drug use currently. One lung adenocarcinoma patient received crizotinib (MET amplification) in 2021, then changed to osimertinib (EGFR exon19del), underwent chemotherapy in 2023, developed hip metastases, and was currently undergoing radiotherapy. Conclusion: This study, for the first time, revealed that MTAPhd were found in approximately 6.8% of Chinese patients across different tumors. Patients with age >= 60, stage III and IV, squamous carcinoma and male, were more likely to occur MTAPhd. Esophageal carcinoma and brain tumor had a higher detection rate. Chinese cohort had lower detection rate of MTAPhd for LUSC and BLCA compared to TCGA cohort. Our results indicated that PRMT5 inhibitors would be a potential therapeutic strategy to be considered for Chinese patients with MTAPhd in the near future. Citation Format: Shuirong Zhang, Wenjin Liu, Mingmin Wang, Caiping Chen, Xiaowei Dong, Aodi Wang, Kai Wang. The profiling of MTAP homozygous deletion (MTAPhd) in a Chinese pan-cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1775.