MTAP
Overview
MTAP (Methylthioadenosine Phosphorylase) is a metabolic enzyme involved in the methionine salvage pathway. MTAP is located at 9p21, a locus frequently deleted alongside CDKN2A and CDKN2B. MTAP loss is therefore a common co-deletion event across multiple cancer types. Loss of MTAP creates a metabolic vulnerability exploitable by MAT2A or PRMT5 inhibitors, making it a therapeutically relevant biomarker.
Alterations observed in the corpus
- MTAP deletions frequently co-occur with CDKN2A and CDKN2B loss at the 9p21 locus across multiple cancer types; confirmed in the breast cancer METABRIC cohort (~2,000 tumors) by integrated CNA-expression analysis PMID:22522925
- Co-deleted with CDKN2A and CDKN2B at 9p21 in urothelial carcinoma (UC); in patient WCM117, CDKN2A/MTAP deletion progressed from sub-clonal heterozygous in the primary to clonal homozygous in distant metastases (FISH-confirmed) PMID:27749842
Cancer types (linked)
- BRCA (Breast cancer): 9p21 deletions encompassing MTAP confirmed in METABRIC cohort; co-deletion with CDKN2A/CDKN2B PMID:22522925
Co-occurrence and mutual exclusivity
- Co-deleted with CDKN2A and CDKN2B at 9p21 in breast cancer PMID:22522925
Therapeutic relevance
- MTAP-deleted tumors are synthetically sensitive to MAT2A and PRMT5 inhibitors due to accumulation of MTA (methylthioadenosine), which inhibits PRMT5 specifically in MTAP-expressing cells. This vulnerability is under clinical investigation but not addressed in the current corpus.
Open questions
- Whether MTAP deletion in breast cancer is an independent driver or purely a passenger co-deletion with CDKN2A is not resolved in the METABRIC analysis.
Sources
This page was processed by entity-page-writer on 2026-05-06. - PMID:27749842
This page was processed by entity-page-writer on 2026-05-15.