Clinicogenomic Landscape of MTAP-Deleted Thoracic Malignancies Across US and Japanese Nationwide Cohorts: Impact of Concurrent CDKN2A Alterations and Driver Mutations - PubMed
4 hours ago
- #thoracic malignancies
- #clinicogenomic analysis
- #MTAP deletion
- MTAP deletion frequency in lung cancer was similar between adenocarcinoma and squamous cell carcinoma in both U.S. and Japanese cohorts, but rare in small cell lung cancer.
- In thymic tumors, MTAP deletion was mostly seen in thymic carcinoma, not thymoma, and was strongly linked to CDKN2A/B deletions.
- MTAP deletion often co-occurred with actionable driver mutations like EGFR, ALK, and ERBB2, but showed an inverse association with RB1 mutations.
- Associations with lower tumor mutational burden and shorter overall survival in EGFR-mutated lung cancer were tied to driver enrichment and CDKN2A loss, respectively.
- Findings support the global development of MTAP-targeted synthetic lethal therapies for thoracic malignancies, especially combined with targeted agents.