WCLC 2025 - Posters & ePosters-P3.14.20 MTAP Deficiency in Thymic Epithelial Tumors

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This study investigated the prevalence of methylthioadenosine phosphorylase (MTAP) deficiency and related genetic alterations in thymic epithelial tumors (TETs), including thymic carcinoma, thymoma, and thymic neuroendocrine tumors. Using retrospective analysis of 100 TET samples profiled by next-generation sequencing at the Dana-Farber Cancer Institute, researchers assessed somatic mutations and copy number alterations (CNAs) in MTAP, CDKN2A, and CDKN2B genes.<br /><br />Results showed that MTAP deficiency, specifically homozygous (two-copy) deletions, was exclusive to thymic carcinoma, occurring in 22.2% of cases, with heterozygous deletions in 14.8%. These deletions co-occurred with frequent loss of CDKN2A and CDKN2B, with dual homozygous deletions of CDKN2A/B present in approximately 30% of thymic carcinoma samples. No MTAP alterations were observed in thymoma or thymic neuroendocrine tumors.<br /><br />The findings highlight that MTAP, CDKN2A, and CDKN2B losses are common genetic events in thymic carcinoma but rare or absent in other TET subtypes. Given that MTAP deficiency has been shown in other cancers to sensitize tumors to protein arginine methyltransferase 5 (PRMT5) inhibitors, these data support exploring targeted PRMT5 inhibitor therapies for MTAP-deficient thymic carcinoma patients.<br /><br />Overall, this research identifies MTAP deficiency as a potential biomarker and therapeutic vulnerability specific to thymic carcinoma among TETs. It suggests a rationale for investigating PRMT5 inhibition as a novel treatment approach in this rare and difficult-to-treat malignancy, which currently has limited options beyond platinum-based chemotherapy.

Asset Subtitle

Jennifer Marks

Meta Tag

Speaker Jennifer Marks

Topic Mesothelioma, Thymoma, and Other Thoracic Tumors

Keywords

MTAP deficiency

thymic carcinoma

thymic epithelial tumors

CDKN2A deletion

CDKN2B deletion

next-generation sequencing

homozygous deletion

protein arginine methyltransferase 5 (PRMT5) inhibitors

biomarker

targeted therapy