An Gang, Xie Zhen-Qing, Li Chang-Hong, Li Qian, Yi Shu-Hua, Qiu Lu-Gui
Chinese Academy of Medical Sciences, Tianjin 300020, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Dec;18(6):1505-10.
Multiple myeloma (MM) is a neoplasm of a terminally differentiated B-cell. Human myeloma cell lines were shown to be suitable model systems for use in various fields of the biological sciences. This study was aimed to investigate the genetic aberrations in human multiple myeloma cell lines. Interphase fluorescence in situ hybridization (FISH) with probes for the regions containing 13q14 (RB-1), 13q14.3 (D13S19), 14q32 (IGHC/IGHV) , 1q12 (CEP1), 17p13 (TP53) were was used to detect 7 HMCL and 85 cases of newly diagnosed MM. FISH with LSI IGH/CCND1 , LSI IGH/FGFR3 and LSI IGH/MAF probes were used to detect t(11;14) (q13;q32) , t(4;14) (p16;q32) and t(14;16) (q32;q23) in HMCL and MM with 14q32 rearrangement. The results showed that molecular cytogenetic aberrations were found in all 7 HMCL, six (85.7%) HMCL simultaneously had 13q14, 13q14.3 deletion. Chromosome 1q21 abnormality was found in six (33.3%) HMCL with at least 3 copies amplifications. Illegitimate 14q32 rearrangement was found in five (71.4%) HMCL, including one with t(11;14), two with t(4;14) and three with t(14;16). 17p13 deletion was detected in 5 HMCL. Chromosomal changes were observed in 85.9% of the 85 cases of newly diagnosed MM. The del(13), 1q12 amplification, del(17p), 14q32 rearrangement, t(11;14), t(4;14), t(14;16) were present in 44.7%, 52.9%, 20%, 62.4%, 27.1%, 24.7% and 3.5% of the patients respectively. There was no significant difference in the prevalence of genetic abnormalities of del(13q), 14q32 rearrangement, 1q12 amplification, t(11;14), t(4;14) except del(17p) and t(14;16). It is concluded that HMCL representative of the most aggressive phase of plasma cell neoplasms accumulated a large amount of genetic aberrations. Loss of p53 are strikingly common in HMCL suggesting that the impairment of the P53 tumor suppressor pathway is an important contributor to extramedullary tumor expansion.
多发性骨髓瘤（MM）是一种终末分化B细胞的肿瘤。人骨髓瘤细胞系被证明是适用于生物科学各个领域的模型系统。本研究旨在调查人多发性骨髓瘤细胞系中的基因畸变情况。使用针对包含13q14（RB - 1）、13q14.3（D13S19）、14q32（IGHC/IGHV）、1q12（CEP1）、17p13（TP53）区域的探针进行间期荧光原位杂交（FISH），以检测7株人骨髓瘤细胞系（HMCL）和85例新诊断的MM。使用LSI IGH/CCND1、LSI IGH/FGFR3和LSI IGH/MAF探针进行FISH，以检测具有14q32重排的HMCL和MM中的t(11;14)(q13;q32)、t(4;14)(p16;q32)和t(14;16)(q32;q23)。结果显示，所有7株HMCL均存在分子细胞遗传学畸变，6株（85.7%）HMCL同时存在13q14、13q14.3缺失。6株（33.3%）HMCL中发现染色体1q21异常，至少有3拷贝扩增。5株（71.4%）HMCL中发现非法的14q32重排，包括1株t(11;14)、2株t(4;14)和3株t(14;16)。5株HMCL中检测到17p13缺失。85例新诊断的MM中，85.9%观察到染色体变化。del(13)、1q12扩增、del(17p)、14q32重排、t(11;14)、t(4;14)、t(14;16)分别出现在44.7%、52.9%、20%、62.4%、27.1%、24.7%和3.5%的患者中。除del(17p)和t(14;16)外，del(13q)、14q32重排、1q12扩增、t(11;14)、t(4;14)的基因异常发生率无显著差异。结论是，代表浆细胞肿瘤最具侵袭性阶段的HMCL积累了大量基因畸变。p53缺失在HMCL中极为常见，表明P53肿瘤抑制途径的损害是髓外肿瘤扩展的重要因素。
