Differences in genetic changes between multiple myeloma and plasma cell leukemia demonstrated by comparative genomic hybridization

Abstract

To analyze the genomic differences between multiple myeloma (MM) and plasma cell leukemia (PCL), a total of 30 cases were studied by comparative genomic hybridization (CGH). In five cases with a low proportion of plasma cells (PC) in bone marrow, an enrichment of PC was performed by using immunomagnetic beads conjugated with the monoclonal antibody B-B4. In 24 out of the 25 MM (96%) and in all five PCL (100%) patients DNA copy number changes were identified by CGH analysis; in the MM case without chromosomal imbalances, the immunomagnetic enrichment of PC had failed. The most recurrent changes in MM patients were gains at chromosomes 15q (48%), 11q (44%), 3q (40%), 9q (40%) and 1q (36%). By contrast, all PCL patients showed gains in 1q. Losses of chromosomal material were significantly more frequent in PCL than in MM patients (P = 0.03): losses on 13q in 80% of PCL vs 28% of MM; and on chromosome 16 in 80% vs 12%, respectively. In addition, PCL patients showed losses of 2q and 6p that were not present in MM. The CGH data show differences in chromosomal imbalances between MM and PCL. Leukemia (2001) 15, 840-845.

Prognostic and biologic significance of chromosomal imbalances assessed by comparative genomic hybridization in multiple myeloma

“…In fact, CGH has proved to be the most robust technique for identification of the total number of chromosome imbalances. [19][20][21][22] This is the first report that shows a prognostic impact of genomic imbalances detected by CGH in MM. Both the presence of genomic changes and the detection of genetic losses were associated with a significant decrease in survival compared with patients without such characteristics.…”

“…22 Calculation of the tumor DNA to normal DNA fluorescence ratios along the length of each chromosome was performed by means of an automated CGH software package (Applied Imaging, Sunderland, United Kingdom). Ratio values obtained from at least 10 metaphase cells for each case were averaged.…”

“…18 CGH studies from our group and others have shown that genomic changes may affect almost all chromosomes, and therefore CGH would be a more appropriate tool than interphase FISH for examining DNA gains and losses globally and to assess the impact of genomic imbalances on survival. [19][20][21][22] Accordingly, the present study was designed to explore the prognostic impact of genetic changes as detected by CGH and evaluate the relationship between these changes and IGH translocation analyzed by FISH.…”

Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt's lymphoma. A cytogenetic and comparative genomic hybridization study

“…Partial or full monosomy of 13 chromosome is usually found in B-cell chronic lymphocytic leukemia 36 and multiple myeloma patients. [37][38][39][40] In NHL, the frequencies of losses on 13q ranged from 4% in follicular lymphomas 23 to 49% in MCL. 7 Gains on 12q as well as losses on 13q have been reported as most frequent in cases with aggressive histopathologic features.…”

Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and increase CKS1B expression in myeloma

“…13 Previously comparative genomic hybridization studies have shown that gains of chromosome 1q consistently involving the 1q21 region is one of the most common genetic abnormalities in MM. [14][15][16] Gain of 1q21 can occur as isochromosomes, duplications or jumping translocations in MM. 17,18 Many of these chromosome changes are structural and do not involve copy number changes.…”