Characteristic recurrent copy number aberrations (CNAs) play a key role in multiple myeloma (MM) pathogenesis and have important prognostic significance for MM patients. Array-based comparative genomic hybridization (aCGH) provides a powerful tool for genome-wide classification of CNAs and thus should be implemented into MM routine diagnostics. We demonstrate the possibility of effective utilization of oligonucleotide-based aCGH in 91 MM patients. Chromosomal aberrations associated with effect on the prognosis of MM were initially evaluated by I-FISH and were found in 93.4% (85/91). Incidence of hyperdiploidy was 49.5% (45/91); del(13)(q14) was detected in 57.1% (52/91); gain(1)(q21) occurred in 58.2% (53/91); del(17)(p13) was observed in 15.4% (14/91); and t(4;14)(p16;q32) was found in 18.6% (16/86). Genome-wide screening using Agilent 44K aCGH microarrays revealed copy number alterations in 100% (91/91). Most common deletions were found at 13q (58.9%), 1p (39.6%), and 8p (31.1%), whereas gain of whole 1q was the most often duplicated region (50.6%). Furthermore, frequent homozygous deletions of genes playing important role in myeloma biology such as TRAF3, BIRC1/BIRC2, RB1, or CDKN2C were observed. Taken together, we demonstrated the utilization of aCGH technique in clinical diagnostics as powerful tool for identification of unbalanced genomic abnormalities with prognostic significance for MM patients.

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Multiple myeloma (MM) is the second most common haematological malignancy. It is characterized by malignant transformation and clonal proliferation of B-lymphocytes with the accumulation of malignant plasma cells in the bone marrow. The incidence of MM increases with age. The average age at presentation is 62 years in men and 61 years in women [1]. Patients below 40 years of age represent less than 3% of all cases. For many years, conventional chemotherapy with combination of melphalan and prednisone was the standard treatment, resulting in overall survival (OS) of approximately 3 years [2]. Currently, high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation is recommended for patients below the age of 65 [3,4]. This treatment extends the OS to 4-5 years [5], with approximately 28% of patients surviving 5 or more years [6]. Despite this relative treatment success, MM remains an incurable disease. Many prognostic factors for MM have been identified. The presence of numerical and/or structural chromosomal aberrations is one of the most important indicators for the prognostic assessments.Due to low proliferation activity of MM cells, conventional cytogenetics detects chromosomal changes in as few as 26-40% of cases [7,8]. In contrast, the technique of interphase fluorescent in situ hybridization (I-FISH) in combination with cytoplasm immunoglobulin staining or immunomagnetic separation of plasma cells enables detection of specific abnormalities in up to 86-98% of patients [9,10,11] Received April 8, 2009Malignant plasma cells in multiple myeloma (MM) are frequently characterized by complex karyotypes and chromosome instability. These cytogenetic changes are considered important prognostic indicators in MM patients. We have studied samples from 68 patients with newly diagnosed MM who were treated with high-dose chemotherapy and autologous stem cell transplantation. G-banding revealed abnormal karyotypes in 14 of 55 patients (25%) who had informative conventional cytogenetics. The combination of cytoplasmic immunoglobulin light chain labeling and interphase fluorescent in situ hybridization (cIg-FISH) revealed the presence of genetic aberrations in 53 of 68 patients (78%). Chromosome 13 abnormalities were found in 33 patients (50%) and IgH rearrangements in 36 patients (56.25%). In IgH positive patients we performed subsequent examinations of IgH affecting translocations t(4;14) and t(11;14) and we found translocation t(11;14) in 8 patients (12.5%) and t(4;14) in 10 patients (15.5%). The occurrences of others chromosomal abnormalities with known prognostic impact in MM were as follows: del(17)(p13) was present in 5 patients (9.8%) and gain 1q21 in 14 patients (36%). Analysis of survival of patients with different cytogenetic abnormalities revealed shorter overall survival (OS) in patients with IgH rearrangements (p=0.020) and trend to shorter OS in patients with gain 1q21 (p=0.064), respectively. Remarkably, patients with two or more aberrations had significantly shorter overall surviva...

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