Comparative genomic hybridization: the profile of chromosomal imbalances in rhabdomyosarcoma

　　比较基因组杂交技术分析横纹肌肉瘤中染色体基因组改变

　　Abstract：Objective To characterize the profile of chromosomal imbalances of rhabdomyosarcoma (RMS). Methods Comparative genomic hybridization (CGH) was used to investigate genomic imbalances in 25 cases of primary RMS including 10 cases of alveolar rhabdomyosarcoma (ARM), 12 cases of embryonic rhabdomyosarcoma (ERMS), 3 cases of polymorphic rhabdomyosarcoma (PRMS) and 2 RMS cell lines (A240 originated from ARMS and RD from PRMS), with correlation to histological type,pathologic grading, clinical staging, gender and age, respectively. Results All twenty-five rhabdomyosarcomas showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. (1) The frequently gained chromosome regions in RMS were 2p, 12q, 6p, 9q,10q, 1p, 2q, 6q, 8q, 15q, 18q, and the frequently lost chromosome regions were 3p, 11p,6p. (2) The frequently gained chromosome arms in ARMS were 12q, 2p, 6, 2q,4q, 10q, 15q. The frequently lost chromosome arms were 3p, 6p, 1q,5q. The frequently gained chromosome regions in ERMS were 7p, 9q,2p,18q,1p,8q. The frequently lost chromosome arms in ERMS were 11p.

　　The frequently gained chromosome arms in translocation associated RMS were 12q, 2, 6, 10q, 4q and 15q(>30%), 3p,6p, 5q (>30%)were the frequently loss chromosome arms. The frequently gained chromosome regions in non-translocation associated RMS were 2p,9q, 18q(>30%), and 11p,14q(>30%) were the frequently loss chromosome regions. Gain of 12q was significantly correlated with the translocation-associated tumors (P<0.05). (4) Gains of 9q was significantly correlated with clinical staging (P<0.05). Conclusions Gain of 2p, 12q,6p ,9q, 10q, 1 p,2q,6q, 8q, 15q, 18q and loss of 3p, 11p,6p may be involved in the tumorigenesis of RMS. Gains of 12q may be correlated with gene fusionromosomal translocation in ARMS. Gains of 9q may be correlated with an early tumor stage of RMS.

　　摘要：目的探讨横纹肌肉瘤(RMS)基因异常情况。方法 比较基因组杂交(CGH)研究横纹肌肉瘤患者基因组改变，25例分别包括10例腺泡状横纹肌肉瘤(ARM),12例胚胎横纹肌肉瘤，3例多态横纹肌肉瘤(PRMS)及2例横纹肌肉瘤细胞系（A240起源于ARMS 及RD 来自于PRMS），及相关组织学类型，病理分级，临床分期，性别和年龄。结果25例中显示1个或更多的基因片段参与复制。（1）这些RMS频繁获得的染色体臂是2p, 12q, 6p, 9q,10q, 1p, 2q, 6q, 8q, 15q, 18q,及频繁丢失的染色体臂是3p, 11p,6p（2）ARMS频繁获得及频繁丢失的的基因片段分别是12q, 2p, 6, 2q,4q, 10q, 15q.和3p, 6p, 1q,5q. ERMS频繁获得及频繁丢失的的基因片段分别是7p, 9q,2p,18q,1p,8q.和11p。（3）与RMS移位频繁获得的基因片段 是12q, 2, 6, 10q, 4q and 15q(>30%),3p,6p, 5q (>30%)是频繁丢失的。与RMS未转移频繁获得的基因片段是2p,9q, 18q(>30%)，和11个p,14p(> 30%)染色体经常缺失的片段。获得的12p明显和肿瘤转移相关(P<0.05).获得的9p明显和临床症状相关(P<0.05).结论获得的2p, 12q,6p ,9q, 10q, 1 p,2q,6q, 8q, 15q, 18q和缺失的 3p, 11p,6p可能参与RMS发生。获得基因融合/染色体易位12p可能与 ARMS转移有关。获得9pk可能与RMS早期分期有关。