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Published on: April 11, 2016
Genomics of MTAP Loss in >500,000 Solid Tumor Specimens Profiled Using Comprehensive Genomic Profiling Platforms
Dean C Pavlick1, Shruthi Rengarajan1, Jessica K Lee2
1Department of Computational Discovery, Foundation Medicine, Inc, Boston, MA.
JCO Precision Oncology
|May 14, 2026
Summary
Methylthioadenosine phosphorylase (MTAP) loss is a common cancer alteration, indicating potential sensitivity to specific inhibitors. Further research is needed for partial MTAP loss cases to clarify clinical benefit.
Area of Science:
- Oncology
- Genomics
- Biomarker Discovery
Background:
- Methylthioadenosine phosphorylase (MTAP) genomic loss is an emerging biomarker for PRMT5 and MAT2A inhibitors.
- The MTAP gene is located on chromosome 9p21.3 near CDKN2A/B.
Purpose of the Study:
- Assess MTAP homozygous loss across tumor types, specific exons lost, MTAP expression, and associated co-alterations.
- Evaluate MTAP loss as a predictive biomarker for targeted therapies.
Main Methods:
- Sequenced 409,755 tissue biopsies and 85,801 liquid biopsies using hybrid capture-based NGS.
- Analyzed genomic alterations, ctDNA tumor fraction, and MTAP gene expression via RNA and DNA sequencing.
Main Results:
- Pan-tumor MTAP loss prevalence was 11.4%, highest in mesothelioma (32.8%), glioma (32.7%), pancreatic (28.9%), and bladder cancers (26.4%).
- Liquid biopsy detection approximated tissue biopsy results with ctDNA TF ≥20%.
- CDKN2A loss was not a reliable proxy for MTAP loss; 33.7% of CDKN2A loss cases lacked MTAP loss.
Conclusions:
- MTAP loss is a frequent pan-tumor alteration predicting potential sensitivity to PRMT5 or MAT2A inhibitors.
- Complete MTAP loss was observed in 82.9%, while 16.5% had partial loss with uncertain clinical benefit.
- The identified co-alteration landscape can inform future clinical trials for MTAP-targeted therapies.
