A pan-cancer analysis of <i>MYC-PVT1</i> reveals CNV-unmediated deregulation and poor prognosis in renal carcinoma

Abstract

// Ioana Posa 1 , Silvia Carvalho 1 , Joana Tavares 1 , Ana Rita Grosso 1 1 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal Correspondence to: Ana Rita Grosso, email: agrosso@medicina.ulisboa.pt Keywords: PVT1, MYC, pan-cancer, KIRC Received: November 17, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: April 28, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: May 19, 2016 ABSTRACT The PVT1 lncRNA has recently been involved in tumorigenesis by affecting the protein stability of the MYC proto-oncogene. Both MYC and PVT1 reside in a well-known cancer-risk locus and enhanced levels of their products have been reported in different human cancers. Nonetheless, the extension and relevance of the MYC- PVT1 deregulation in tumorigenesis has not yet been systematically addressed. Here we performed a pan-cancer analysis of matched copy number, transcriptomic, methylation, proteomic and clinicopathological profiles for almost 7000 patients from 17 different cancers represented in the TCGA cohorts. Among all cancers types, kidney renal clear cell carcinoma (KIRC) showed the strongest upregulation of PVT1 and increased levels of both MYC and PVT1 correlated with the clinical outcome. PVT1 misregulation in KIRC is mostly associated to promoter hypomethylation rather than locus amplification. Furthermore, we found an association between MYC levels and PVT1 expression, which impacted on MYC-target genes. Collectively, our study discloses the role of PVT1 as a novel prognostic factor and as a molecular target for novel therapeutic interventions in renal carcinoma.