Analysis of NAPRT genetic variants and gene expression in tumors

Nicotinate phosphorybosyltransferase (Naprt) is an emerging target in cancer therapy, as Naprt loss is associated with EMT phenotype. Whether this is due to mutations in the gene is largely unknown. To study the role of NAPRT variants in the regulation of gene expression, we analyzed CNV (copy number variation) and eQTLs (expression quantitative trait loci) that alter the expression of NAPRT in tumor samples from the PanCancer project of The Cancer Genome Atlas (TCGA). We obtained NAPRT gene expression and CNV data from the cBioPortal and single-tissue cis-eQTL data from the PancanQTL database. In 16 types of cancer, we analyzed the correlation between CNV and expression, and the number and effect of eQTLs in NAPRT and surrounding genes. Most of the studied cancer types through the cBioPortal had no NAPRT alteration in more than 80% of the samples. Amplification of the locus was the most common alteration, though it did not fully overlap with gene upregulation. Ovarian cancer was the exception with NAPRT amplified in 33% and upregulated in 58% of those cases. In the PancanQTL database, we found several NAPRT eQTLs that were not reported in GTEx, which comprises non-pathological samples, meaning that these might be cancer specific variants. LGG (low grade glioma) had 38 specific variants and 18 more were present in several cancer types. For example, rs34979030 is common to 11 different types of cancer. On the other hand, rs10099003 appears to influence NAPRT gene exclusively in prostate cancer. Though NAPRT gene has a high number of genetic variants, their frequency in cancer is low. However, some have important effects on gene expression and might be cancer specific, stressing the need to characterize NAPRT gene expression to improve patient stratification for tailored therapeutics.