Molecular landscape of splicing dysregulation in pheochromocytomas and paragangliomas

#3859

Introduction: Pheochromocytomas and paragangliomas (PPGL) are commonly benign neuroendocrine tumors (NETs). However, up to 25 % of patients develop metastases or aggressive behaviour. Genomic characterization current classifies PPGL into different genetic clusters, yet there are no biomarkers which could stratify patients based on their prognosis. The dysregulation of the splicing process has emerged as a novel feature, common in most cancers, and linked to a more aggressive phenotype in several tumors, including NETs, but this process has not been examined in detail in PPGL.

Aim(s): The aim of this work was to determine the splicing machinery profile in PPGL, its association with clinical/molecular features, and to explore the functional role of splicing inhibitors in vitro.

Materials and methods: We explored the expression of 310 splicing-related genes in the TCGA dataset and studied their relation with clinical data. As in vitro models, we used human neuroblastoma cells, SK-N-AS (wildtype and SDHB knock-down), and the rat pheochromocytoma cell line, PC12. To inhibit the splicing process, we used Pladienolide B, a SF3B1 inhibitor.

Conference:

Presenting Author:

Authors: Moreno Montilla M, Blázquez-Encinas R, Martínez Montes �, García Vioque V, Alors-Pérez E,

Keywords: pheochromocytoma, paraganglioma, splicing dysregulation, splicing machinery, pladienolide B,