Bridge Julia A, Liu Jian, Qualman Stephen J, Suijkerbuijk Ron, Wenger Gail, Zhang Ji, Wan Xiaoying, Baker K Scott, Sorensen Poul, Barr Frederic G
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Genes Chromosomes Cancer. 2002 Mar;33(3):310-21. doi: 10.1002/gcc.10026.
In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.
在本研究中，我们选取了伴有或不伴有间变特征的PAX3/FKHR和PAX7/FKHR融合转录本阳性及阴性的肺泡状横纹肌肉瘤（ARMS）和胚胎性横纹肌肉瘤（ERMS），以确定这些组织病理学和基因性横纹肌肉瘤（RMS）变异型之间基因组失衡的差异和/或相似性。对45例横纹肌肉瘤标本进行了比较基因组杂交（CGH）和荧光原位杂交（FISH）研究，其中包括23例ARMS和22例ERMS（12例ERMS病例来自早期研究）。RMS的间变变异型此前未进行过CGH分析。总体而言，最显著的失衡包括染色体或染色体区域2/2q（40%）、7/7q（31%）、8/8p（53%）、11/11q（31%）、12q13 - 15（49%）、13q14（22%）和20/20p（31%）的增加，以及1p36（27%）、3p14 - 21（22%）、9q21 - 22（33%）、10q22 - qter（18%）、16q（27%）、17p（22%）和22（22%）的缺失。这些增减在ARMS和ERMS组织学亚型之间分布均匀（不包括主要在ERMS中观察到的7/7q和1 / 11q增加），表明这些实体在复发性基因组失衡方面相似。此外，基因组失衡在ARMS融合转录本子型中也均匀分布，这为尽管在某些情况下不存在融合转录本但仍存在遗传亲缘关系提供了证据。分别在26%的ARMS病例和23%的ERMS病例中检测到基因组扩增（后者几乎所有亚组都表现出间变特征）。一个涉及15q25 - 26的扩增子对应于胰岛素样生长因子I型受体（IGF1R）基因的位点。在表现出15q25 - 26扩增子的病例中通过分子方法证实了IGF1R的扩增。总之，这些结果表明，在横纹肌肉瘤的组织病理学和基因亚型中，基因组的增加和缺失涉及相似的染色体且频率相近，基因组扩增不仅在横纹肌肉瘤的肺泡组织学亚型中常见，在伴有间变的ERMS中也常见，并且IGF1R的扩增可能在一部分横纹肌肉瘤的发生或进展中起作用。
