Drach J, Schuster J, Nowotny H, Angerler J, Rosenthal F, Fiegl M, Rothermundt C, Gsur A, Jäger U, Heinz R
First Department of Internal Medicine, University of Vienna, Austria.
Cancer Res. 1995 Sep 1;55(17):3854-9.
Because metaphase cytogenetic studies in multiple myeloma (MM) are hampered by a low proliferative activity of myeloma cells in vitro, interphase cytogenetics by means of fluorescence in situ hybridization (FISH) should improve the detection of chromosomal abnormalities in MM. We therefore investigated chromosomal aneuploidy in 36 patients with MM using interphase FISH and alpha-satellite DNA probes for chromosomes 1, 3, 7, 8, 11, 12, 16, 17, 18, and X. By FISH, myeloma cells from 32 patients (88.9%) were aneuploid for at least one of the chromosomes examined. In 24 patients (66%), aberrations of > or = 3 chromosomes were observed. Aneuploidy was predominantly characterized by a gain of chromosome numbers, with involvement of chromosomes 3, 7, and 11 occurring in > 50% of patients. Loss of a centromeric signal suggesting monosomy was most frequently observed for chromosomes 17 (22.2% of patients) and X (monosomic in 42.3% of female patients, but loss of chromosome X was never observed in males, P < 0.05). Dual-color FISH studies provided evidence for marked heterogeneity of aneuploid cells in 8 patients (22.8%). Occurrence of chromosomal aneuploidy was independent of stage and pretreatment status. Gain of chromosome 3 was significantly correlated with an IgA paraprotein (P < 0.05). In 12 patients, the direct comparison of metaphase cytogenetics and FISH showed that FISH detected aneuploidy of chromosomes in 9 patients that was missed by metaphase analysis. In conclusion, interphase FISH, by which chromosomal aneuploidy was detected in almost 90% of patients with MM, represents an approach for evaluating the clinical significance of specific chromosomal abnormalities in MM.
由于多发性骨髓瘤（MM）的中期细胞遗传学研究受到骨髓瘤细胞体外增殖活性低的阻碍，因此通过荧光原位杂交（FISH）进行的间期细胞遗传学研究应能提高MM中染色体异常的检测率。因此，我们使用间期FISH和针对1、3、7、8、11、12、16、17、18号染色体及X染色体的α-卫星DNA探针，对36例MM患者的染色体非整倍性进行了研究。通过FISH检测发现，32例患者（88.9%）的骨髓瘤细胞至少对其中一条检测染色体呈非整倍性。在24例患者（66%）中，观察到≥3条染色体的畸变。非整倍性主要表现为染色体数目增加，超过50%的患者出现3、7和11号染色体受累。提示单体性的着丝粒信号缺失最常见于17号染色体（22.2%的患者）和X染色体（42.3%的女性患者为单体性，但男性患者未观察到X染色体缺失，P<0.05）。双色FISH研究为8例患者（22.8%）非整倍体细胞的显著异质性提供了证据。染色体非整倍性的发生与分期和预处理状态无关。3号染色体增加与IgA副蛋白显著相关（P<0.05）。在12例患者中，中期细胞遗传学与FISH的直接比较显示，FISH检测到9例患者的染色体非整倍性，而中期分析未发现。总之，间期FISH能在近90%的MM患者中检测到染色体非整倍性，是评估MM中特定染色体异常临床意义的一种方法。
