Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes
Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes
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DOI：
10.1002/gcc.10026
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发表时间：
2002-03-01
影响因子：
3.7
通讯作者：
Barr, FG
中科院分区：
文献类型：
--
作者：
Bridge, JA;Liu, J;Barr, FG
在这项研究中，我们选择了具有或不具有间变特征的PAX3/FKHR和PAX7/FKHR融合转录物阳性和阴性的肺泡横纹肌肉瘤（ARMS）和胚胎性横纹肌肉瘤（ERMS）。以确定这些组织病理学和遗传性横纹肌肉瘤（RMS）变异中基因组不平衡的差异和/或相似性。对 45 个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 个 ARMS 和 22 个 ERMS（早期研究中纳入了 12 个 ERMS 病例）。 RMS 的间变性变体之前尚未进行过 CGH 分析。总体而言，最突出的不平衡是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的损失(27%)、3p14-21 (22%)、9q21-22 (33%)、10q22-qter (18%)、16q (27%)、17p (22%) 和 22 (22%)。这些增益和损失在 ARMS 和 ERMS 组织学亚型之间平均分布（不包括主要在 ERMS 中观察到的 7/7q 和 11/11q 增益），表明这些实体在复发性基因组失衡方面是相似的。此外，基因组失衡也均匀分布在 ARMS 融合转录本亚型中，尽管在某些情况下不存在融合转录本，但为遗传亲缘关系提供了证据。分别在 26% 和 23% 的 ARMS 和 ERMS 病例中检测到基因组扩增（几乎所有后者都表现出间变性特征）。一个涉及 15q25-26 的扩增子对应于 I 型胰岛素样生长因子受体 (IGF/R) 基因的位点。在显示 15q25-26 扩增子的病例中，IGF/R 的扩增得到分子证实。总之，这些结果表明，在横纹肌肉瘤的组织病理学和遗传亚型中，基因组的获得和丢失涉及频率相似的相似染色体，基因组扩增不仅在横纹肌肉瘤的肺泡组织学亚型中很常见，而且在伴有退行性变的ERMS中也很常见。 IGF/R 的扩增可能在部分横纹肌肉瘤的发生或进展中发挥作用。 (C) 2002 Wiley-Liss, Inc.
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 (IGF/R) gene. Amplification of IGF/R 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 IGF/R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas. (C) 2002 Wiley-Liss, Inc.