Clinicogenomic Landscape of MTAP-Deleted Thoracic Malignancies Across US and Japanese Nationwide Cohorts: Impact of Concurrent CDKN2A Alterations and Driver Mutations
Consistent DNA deletion patterns across US and Japanese lung cancers reveal promising targets for new combination therapies.
Analysis of 15,942 thoracic cancer samples across AACR GENIE (US, n=11,091) and C-CAT (Japan, n=4,851) confirms comparable MTAP deletion prevalence (8-20%) in lung adenocarcinoma and squamous cell carcinoma, with strong association to CDKN2A/B loss and frequent co-occurrence with actionable EGFR/ALK/ERBB2 alterations. These findings establish a reproducible, cross-population target landscape supporting the rational development of MTAP synthetic lethal combination therapy.
What the study was
- Study design
- Retrospective multinational cohort study
- Population
- Thoracic cancer patients (lung, pleural, thymic tumors)
- Sample size
- 15942
- Category
- Genomics/Precision Medicine
- Maturity
- Validated
- Journal
- JCO Precision Oncology
Why it surfaced
First large-scale cross-national (US+Japan, n~16K) clinicogenomic landscape of MTAP-deleted thoracic tumors. Directly supports development of MTAP synthetic lethal strategies — a promising emerging target class. Actionable driver co-occurrence data highly relevant to therapy combinations. JCO Precis Oncol.
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