High-Resolution Assessment of Gains and Losses of Chromosomes in Patients with Multiple Myeloma Treated with Bortezomib.

Multiple myeloma is a disease of the antibody producing plasma cells in the bone marrow. It has been characterized by frequent genomic alterations including gains and losses of chromosomes. Some of these alterations result in poor clinical prognosis. Bortezomib, a first in class proteasome inhibitor, is approved for the treatment of relapsed multiple myeloma. To better understand how the genome wide changes observed in myeloma relate to prognosis and treatment response, we have used single nucleotide polymorphism (SNP) array technology to assess genotypes and DNA copy number at up to 100,000 genomic loci. DNA from 147 bone marrow tumor biopsies collected in multi-center phase II and III clinical trials of relapsed multiple myeloma patients prior to treatment with Bortezomib were hybridized on SNP arrays to assess genomic aberrations. Commonly seen genomic alterations in myeloma were observed, including deletions of chromosome 13 (37%), 1p (25%), 6q (23%), and amplifications on 1q (35%). We found that 35% of this relapsed myeloma population exhibited a hyperdiploid genome characterized by gains of chromosomes 3, 5, 7, 9, 11, 15, and 19. Other notable genomic deletions included 17p (22%), 8p (27%) and 10p (16%). A correlation of response to bortezomib therapy in patients with differential gains and losses at the chromosomal level is ongoing. Consistent with previous reports, response to bortezomib was observed in patients with poor prognostic chr 13 deletions. A more in-depth analysis of specific loci associated with clinical outcome will be discussed. In summary, this data will help further define genomic aberrations in multiple myeloma and their association with treatment outcome.