Molecular heterogeneity and centrosome-associated genes in multiple myeloma

Fedor Kryukova*, Pavel Nemeca*, Elena Dementyevaa*, Lenka Kubiczkovaa, Ivana Ihnatovab, Eva Budinskab, Jiri Jarkovskyab, Sabina Sevcikovaae, Petr Kuglikac & Roman Hajek*adea Babak Myeloma Group, Department of Pathological Physiologyb Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republicc Integrated Laboratory of Molecular Cytogenetics, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republicd Department of Internal Medicine – Hematooncologye Department of Clinical Hematology, University Hospital Brno, Czech Republic*These authors contributed equally to this manuscript.Correspondence: Roman Hajek, Kamenice 5, 62500 Brno, Czech Republic. Tel: +420773242892. Fax: +420549494340. E-mail: roman.hajek@fno.czAbstractIn multiple myeloma (MM), biologic complexity originates from complex oncogenic processes involving somatic acquisition of myriad mutations coupled with genetic variability within the host. This pathogenically determined molecular heterogeneity predetermines clinical intricacy. In this study, we performed gene expression profiling (GEP) focusing on centrosome-related genes to determine the molecular heterogeneity for centrosome-associated genes in patients with MM. We identified the gene pattern with an impact on myeloma pathogenesis. According to expression tendency, three subgroups of patients were established. The revealed molecular signature is related to overall survival as well as to clinical parameters and the International Staging System. Associations with integral clinical parameters allow us to proclaim the impact of the revealed functional gene set in MM genesis. We believe that future investigation of this molecular heterogeneity will help to refine the broad prognoses offered by present-day established systems and even sub-stratify them.