The mutational profile in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. (R-9069)

Multiple myeloma (MM), also called Kahler's disease or plasma cell myeloma, is an incurable plasma cell cancer in the bone marrow (BM). Plasma cells are white blood cells, responsible for the antibody production. The expansion of these cells leads to an overproduction of antibodies, resulting in symptoms as anemia and bone lesions. All cases of MM are preceded by an asymptomatic, non-malignant prestage, called monoclonal gammopathy of undetermined significance (MGUS). This prestage has an annual risk of 1% to develop MM. Despite efforts to elucidate the molecular mechanisms of the MGUS-to-MM progression, its pathogenesis remains largely unknown. Therefore, this proposal aims to investigate the somatic mutations underlying the progression from MGUS to MM. An unique collection of biobank-stored samples will be used and studied by Next-Generation Sequencing (NGS) on separate patient cohorts as well as on serial samples. Serial BM smears from MGUS patients with and without MM progression will be sequenced, allowing to identify the evolutionary mechanisms of critical driver gene mutations. These mutated genes can have a potential value in the clinical practice as biomarker(s) to predict which MGUS patients will progress to MM and which not.

Keywords:AUTOIMMUNE DISEASES

Disciplines:Immunology, Laboratory medicine, Medical systems biology, Molecular and cell biology