High frequencies of chromosomal aberrations in multiple myeloma and monoclonal gammopathy of undetermined significance in direct chromosome preparation

• Published in: British journal of haematology Vol. 126; no. 4; pp. 487 - 494
• Main Authors: Nilsson, Therese, Lenhoff, Stig, Rylander, Lars, Höglund, Mattias, Turesson, Ingemar, Mitelman, Felix, Westin, Jan, Johansson, Bertil
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2004; Blackwell; Blackwell Publishing Ltd
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Bone Marrow Cells - pathology; Chromosome Aberrations; Clinical Medicine; Demecolcine; direct preparation; Female; Hematologi; Hematologic and hematopoietic diseases; Hematology; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; In Situ Hybridization, Fluorescence; karyotype; Karyotyping - methods; Klinisk medicin; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; monoclonal gammopathy of undetermined significance; Multiple Myeloma - genetics; myeloma; Paraproteinemias - genetics; Chromosomal aberration; Immunopathology; Hematology; Chromosome; Malignant hemopathy; Myeloma; Monoclonal gammopathy of undetermined significance; Immunoglobulinopathy; Lymphoproliferative syndrome; Cytogenetics; Frequency; Karyotype; direct preparation
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2004.05060.x

Summary Although many cases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are cytogenetically normal, interphase fluorescence in situ hybridization (FISH) analyses reveal aberrations in the majority of the cases. Most likely, non‐neoplastic cells are more prone to divide in culture than neoplastic cells. Direct chromosome preparations (DCP) would be one way to circumvent this methodological problem. We have investigated 47 bone marrow samples from 39 patients by DCP. A median of 58 metaphases (range 9–158) was analysed per sample. Interphase FISH analyses using probes to detect IGH rearrangements, ‐13/13q‐, +3, +7, and +11 were also performed. Abnormal karyotypes were detected in 15 (63%) of 24 MM and in 4 (50%) of eight MGUS/smouldering MM (SMM) cases that could be successfully cytogenetically analysed. Age, sex, or degree of bone marrow plasma cell (PC) infiltration did not influence the karyotypic patterns (P > 0·05). However, the frequencies of aberrant karyotypes varied in relation to the Colcemide concentrations used – 7% (30 ng/ml) versus 69% and 67% (100 and 200 ng/ml, respectively) (P = 0·01). Combining the G‐banding and FISH results, abnormalities were detected in 29 of 31 (94%) MM and in six of eight (75%) MGUS/SMM patients. Thus, cytogenetic and FISH analyses after DCP using 100–200 ng Colcemide/ml identified aberrations in most MM/MGUS/SMM, irrespective of PC percentages.