Chromosomal and genetic abnormalities in myeloma

Chromosomal translocations are a hallmark of lymphoid tumours. Multiple myeloma (MM) is a tumour of the plasma cell, the terminally differentiated B lymphoid cell. In recent years, a large number of chromosomal and genetic abnormalities have been detected in myeloma, the most prominent being chromosome 13q deletions and translocations affecting the immunoglobulin heavy chain (IgH) locus on chromosome 14q32. The latter involve a large array of chromosomal partners, from which multiple oncogenes have been proposed as candidates for dysregulation. In addition, a wide variety of changes including numerical aberrations, translocations involving loci other than the immunoglobulin genes, and aberrations of known oncogenes such as N-ras mutations, have been found. With the refinement of molecular cytogenetic techniques, the sensitivity of detecting these molecular abnormalities is continuing to increase. However, with the exception of 13q deletions which have been consistently associated with an adverse prognosis, the role of the other changes in the pathogenesis of MM, and their effect on disease behaviour and prognosis are still being clarified. In this review, we will discuss the most common molecular abnormalities found in primary MM and cell lines, and consider the available evidence for a pathogenic role in MM.