Joos Stefan, Granzow Martin, Holtgreve-Grez Heidi, Siebert Reiner, Harder Lana, Martín-Subero José I, Wolf Jürgen, Adamowicz Martyna, Barth Thomas F E, Lichter Peter, Jauch Anna
German Cancer Research Center, H0700, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Int J Cancer. 2003 Feb 10;103(4):489-95. doi: 10.1002/ijc.10845.
Four Hodgkin's lymphoma cell lines (KM-H2, HDLM-2, L428, L1236) were analyzed for cytogenetic aberrations, applying multiplex fluorescence in situ hybridization, chromosome banding and comparative genomic hybridization. Each line was characterized by a highly heterogeneous pattern of karyotypic changes with a large spectrum of different translocated chromosomes (range 22-57). A recurrent finding in all cell lines was the presence of chromosomal rearrangements of the short arm of chromosome 2 involving the REL oncogene locus. Furthermore, multiple translocated copies of telomeric chromosomal segments were frequently detected. This resulted in a copy number increase of putative oncogenes, e.g., JAK2 (9p24) in 3 cell lines, FGFR3 (4p16) and CCND2 (12p13) in 2 cell lines as well as MYC (8q24) in 1 cell line. Our data confirm previous cytogenetic results from primary Hodgkin's tumors suggesting an important pathogenic role of REL and JAK2 in this disease. In addition, they provide evidence for a novel cytogenetic pathomechanism leading to increased copy numbers of putative oncogenes from terminal chromosomal regions, most probably in the course of chromosomal stabilization by telomeric capture.
应用多重荧光原位杂交、染色体显带和比较基因组杂交技术,对4种霍奇金淋巴瘤细胞系(KM-H2、HDLM-2、L428、L1236)进行细胞遗传学畸变分析。每个细胞系的核型变化模式高度异质性,存在大量不同的易位染色体(范围为22 - 57条)。所有细胞系中反复出现的一个现象是,2号染色体短臂发生涉及REL癌基因位点的染色体重排。此外,还经常检测到端粒染色体片段的多个易位拷贝。这导致了假定癌基因的拷贝数增加,例如,3个细胞系中JAK2(9p24)、2个细胞系中FGFR3(4p16)和CCND2(12p13)以及1个细胞系中MYC(8q24)。我们的数据证实了先前原发性霍奇金肿瘤的细胞遗传学结果,表明REL和JAK2在该疾病中具有重要的致病作用。此外,它们还为一种新的细胞遗传学发病机制提供了证据,该机制导致来自染色体末端区域的假定癌基因拷贝数增加,很可能是在通过端粒捕获实现染色体稳定的过程中发生的。