FIGURE 3.

Identification and functional characterization of PVT1. PVT1 was identified in murine lymphomas following the observation of translocations, viral insertions, and amplifications involving the Pvt1 locus. Functional characterization of PVT1 has utilized various loss‐of‐function (LOF) and gain‐of‐function (GOF) models including amplification genetically engineered mouse models (GEMMs) (Myc/Pvt1^AMP, Myc^AMP, ¹⁴⁵ ), locus deletion (PVT1^Δ), tumor‐specific mutagenesis of the Pvt1‐associated p53 Response Element (p53RE) (Δp53RE, ¹⁰³ ), transcript degradation with RNAi and ASO, and CRISPR‐mediated epigenetic activation and inhibition (CRISPRa/i). The increased tumor growth observed in a Myc/Pvt1 co‐amplification GEMM (Myc/Pvt1^AMP) compared to Myc amplification alone (Myc^AMP) when crossed to the MMTV‐Neu BC (breast cancer) GEMM suggests an oncogenic function for Pvt1 (red box, ¹⁴⁵ ). However, the increased tumor growth in Pvt1‐associated p53RE mutagenized lung tumors following Cre‐mediated tumor initiation in a Kras‐driven lung adenocarcinoma (LUAD) GEMM suggests a tumor suppressor function (green box, ¹⁰³ )