Analysis of Familial Dysglobulinemia: a Multicenter IFM Study.

Abstract 4891

Multiple myeloma is a haematological malignancy which rarely occurs in a familial context. MGUS corresponds to the existence of a clone secreting a monoclonal immunoglobulin and can in some patients evolve to multiple myeloma. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of multiple myeloma, there are presently no identified genetic mechanisms which contribute to myelomagenesis, in particular in familial cases. The identification and study of families with several cases of dysglobulinemia should contribute to the determination of genetic factors predisposing to multiple myeloma. The aim of this study is to identify genetic factors predisposing to familial dysglobulinemia, thanks to the establishment of a DNA bank. Peripheral blood samples were collected both from patients with dysglobulinemia and from healthy family members and lymphoblastoid lines established for further studies. For this purpose, we have initiated a multicenter study aiming to identify families with several cases of dysglobulinemia, including both multiple myeloma and/or Monoclonal Gammapathy of Undetermined Significance (MGUS). This effort is supported by a French National Programme Hospitalier de Recherche Clinique (PHRC) and the French National Institute for Cancer Research (INCa)., and involves the French multicentric Myeloma groups, Intergroupe Francophone du Myélome (IFM) and Myeloma Autograft Group (MAG), in coordination with the Réseau des Hémopathies Familiales. This study was activated in Octobrer 2007 and as of April 2009, 72 families with at least two cases of dysglobulinemia (median 2, range 2-5) have been identified. Among 166 cases of dysglobulinemia, 100 were diagnosed as multiple myeloma, 49 as MGUS and the remainder as light chain amyloidosis or Waldenstrom's disease. The sex ratio was 1:1 for all groups. The median range at inclusion in this study was 64 years (range 33-85 years). The heavy chain subtype distribution was classical, with a majority of IgG cases. 42% of cases corresponded to cases involving parents and offspring and 54% corresponded to cases involving siblings. This study is ongoing in order to collect samples from 100 families and to initiate genetic analyses to identify predisposing factors.