The role of epigenetic regulation in B-cell lymphomas

Resumen

There is increasing evidences showing that cancer is not only a genetic disease but also an epigenetic disease. The most important epigenetic regulators are the Polycomb and trithorax complexes and DNA methylation. Moreover several cancers show altered expression of microRNAs that also deregulate several genes. In this work, we have undertaken the study of SUZ12, a Polycomb group protein and the microRNAs (miRNA) expressed by the oncogenic Epstein Barr Virus (EBV) in different B-cell lymphoma types. SUZ12 is a component of the Polycomb PRC2 complex, along with EZH2, that has been involved in embryonic stem cell differentiation. Various results coincide in showing that EZH2 plays an essential role in many cancer types, but this has not been as fully demonstrated for SUZ12. In the first part of this work, we report SUZ12 protein expression and genetic alterations in several tumors and especially in Mantle Cell Lymphoma (MCL), a tumor whose pathogenesis is not completely understood. Additionally, functional and genomic studies demonstrate that SUZ12 targets genes involved in central oncogenic pathways are associated with MCL pathogenesis and SUZ12 deficiency results in reduced viability of MCL cells. Our results support the hypothesis that the abnormal expression of SUZ12 in MCL may account for some of the still unexplained features of MCL, and lead us to propose a putative oncogenic role for SUZ12. These data suggest that drugs targeting the PRC2 complexes, such as LBH589, could be a rational therapeutic approach for MCL patients.