Smetana J, Fröhlich J, Vranová V, Mikulásová A, Kuglik P, Hájek R
Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Czech Republic.
Klin Onkol. 2011;24 Suppl:S43-8.
Multiple myeloma (MM) is a hematological disease caused by malignant proliferation of clonal plasma cells (PCs) known for its clinical and biological heterogeneity. Identification of chromosomal changes in genome of PCs plays a key role in MM pathogenesis and is supposed to have important prognostic significance for MM patients. There are two major genetic entities in MM. Hyperdiploid tumors (H-MM), which include about 50% of MM tumors, often have multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21 and a substantially lower prevalence of IgH translocations. Nearly half of tumors are non-hyperdiploid (NH-MM), and mostly have one of five recurrent IgH translocations: 11ql13 (CCND1), 6p21 (CCND3), 16q23 (MAF), 20q12 (MAFB), and 4p16 (FGFR3 and MMSET). The development and expanded use of new technologies, such as genome-wide array-based comparative genomic hybridization (aCGH) has accelerated genomic research in MM. This technique is a powerful tool to globally analyze recurrent copy number changes in tumor genome in a single reaction and to study cancer biology and clinical behaviors. It widely overcame routinely used cytogenetic techniques (G-banding, FISH) both in minimal resolution of chromosomal changes and amount of obtained genomic data important for further analyses and clinical applications. Array CGH technique is now used to better understanding of molecular phenotypes, sensitivity to particular chemotherapeutic agents, and prognosis of these diseases. This paper brings brief literature and methodic overview of oligonucleotide-based array-CGH technique in MM diagnosis.
多发性骨髓瘤(MM)是一种由克隆性浆细胞(PC)恶性增殖引起的血液系统疾病,以其临床和生物学异质性而闻名。鉴定PC基因组中的染色体变化在MM发病机制中起关键作用,并且被认为对MM患者具有重要的预后意义。MM中有两种主要的遗传实体。超二倍体肿瘤(H-MM)约占MM肿瘤的50%,通常有涉及3、5、7、9、11、15、19和21号染色体的多个三体,且IGH易位的发生率显著较低。近一半的肿瘤是非超二倍体(NH-MM),大多具有五种常见的IGH易位之一:11q113(CCND1)、6p21(CCND3)、16q23(MAF)、20q12(MAFB)和4p16(FGFR3和MMSET)。新技术如基于全基因组阵列的比较基因组杂交(aCGH)的发展和广泛应用加速了MM的基因组研究。该技术是一种强大的工具,可在单一反应中全面分析肿瘤基因组中反复出现的拷贝数变化,并研究癌症生物学和临床行为。它在染色体变化的最小分辨率和对进一步分析及临床应用重要的获得的基因组数据量方面都广泛克服了常规使用的细胞遗传学技术(G显带、FISH)。阵列CGH技术现在用于更好地理解这些疾病的分子表型、对特定化疗药物的敏感性和预后。本文简要介绍了基于寡核苷酸的阵列CGH技术在MM诊断中的文献和方法概述。