NAPRT
Overview
NAPRT (Nicotinate Phosphoribosyltransferase) encodes a key enzyme in the Preiss-Handler NAD+ biosynthesis pathway, converting nicotinic acid (niacin) to nicotinate mononucleotide. NAPRT expression enables tumors to survive inhibition of NAMPT (the primary NAD+ synthesis enzyme), making NAPRT status a predictive biomarker for NAMPT inhibitor sensitivity. In muscle-invasive bladder cancer, NAPRT was identified as epigenetically silenced by promoter hypermethylation.
Alterations observed in the corpus
- NAPRT was epigenetically silenced in 13% of muscle-invasive bladder cancer (MIBC) tumors (n=412) by promoter DNA hypermethylation with concordant loss of expression, identified in a set of 158 epigenetically silenced genes by integrated methylation-expression analysis PMID:28988769
Cancer types (linked)
- BLCA (Bladder Urothelial Carcinoma): NAPRT silenced by promoter hypermethylation in 13% of MIBC; silencing occurred without somatic mutation in NAPRT, distinguishing it from classical tumor suppressors altered via both mechanisms PMID:28988769
Co-occurrence and mutual exclusivity
Therapeutic relevance
- Epigenetic silencing (and thus loss) of NAPRT in 13% of MIBC tumors would render those tumors more sensitive to NAMPT inhibitors, as NAPRT-deficient cells cannot use the Preiss-Handler rescue pathway to maintain NAD+ levels during NAMPT inhibition.
Open questions
- Whether NAPRT silencing correlates with specific MIBC molecular subtypes (luminal vs. basal-squamous) is not reported in the corpus; prospective validation of NAPRT as a biomarker for NAMPT inhibitor sensitivity in bladder cancer is needed.
Sources
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