PVT1 Splice Variants in Medulloblastoma

Example 1

The ENSEMBLE database was searched in order to identify the variants that regulate MYC protein in cancer cells. Accordingly, 25 splice variants of PVT1 have been found (FIG. 2). Primers were developed to identify the abundance of each transcript in patient derived medulloblastoma (MB) xenografts (PDX) (FIGS. 3 and 4). The analysis suggested that PVT1_212 is the most abundant PVT1 splice variant in all the 4 subgroups of the MB PDXs, while PVT1_203 being the second most prevalent splice variant. PVT1_212 is most prevalent in the MB Subgroup 3 patients, which has the poorest prognosis among the MB patients (FIG. 5). Three types of PVT1_212 expression pattern were identified in MB PDXs as well in patient samples: Low PVT1_212 expressing group (0-15×): contained mainly Subgroup 4 MBs, Intermediate PVT1_212 expressing group (15-200×): contained Subgroups 3, Shh and Wnt MB, and the high PVT1_212 expressing group (200-1000×): Exclusively Subgroup 3 (FIGS. 6 and 7). This demonstrated that PVT1 expression can be used to stratify MB patients, where the high PVT1_212 expressing group (200-1000×) can designate the 8q24 gain, MYC-driven type of the Group 3 MB patients (generally associated with the poor prognosis).