Panagopoulos Ioannis, Mertens Fredrik, Isaksson Margareth, Domanski Henryk A, Brosjö Otte, Heim Sverre, Bjerkehagen Bodil, Sciot Raf, Dal Cin Paola, Fletcher Jonathan A, Fletcher Christopher D M, Mandahl Nils
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
Genes Chromosomes Cancer. 2002 Dec;35(4):340-52. doi: 10.1002/gcc.10127.
Extraskeletal myxoid chondrosarcoma (EMC) is a soft-tissue neoplasm cytogenetically characterized by the translocations t(9;22)(q22;q11-12) or t(9;17)(q22;q11), generating EWS/CHN or RBP56/CHN fusion genes, respectively. In the present study, 18 EMCs were studied both cytogenetically and at the molecular level. Chromosomal aberrations were detected in 16 samples: 13 with involvement of 9q22 and 22q11-12, and three with rearrangements of 9q22 and 17q11. Fifteen cases had an EWS/CHN fusion transcript and three had an RBP56/CHN transcript. The most frequent EWS/CHN transcript (type 1; 10 tumors), involved fusion of EWS exon 12 with CHN exon 3, and the second most common (type 5; two cases) was fusion of EWS exon 13 with CHN exon 3. In all tumors with RBP56/CHN fusion, exon 6 of RBP56 was fused to exon 3 of CHN. By genomic XL PCR and sequence analyses, the breakpoints from 14 cases were mapped in the EWS, RBP56, and CHN genes. In CHN, 12 breakpoints were found in intron 2 and only two in intron 1. In EWS, the breaks occurred in introns 7 (one break), 12 (eight breaks), and 13 (one break), and in RBP56 in intron 6. Repetitive elements such as Alu and LINE sequences seem to have limited, if any, importance in the genesis of EWS/CHN and RBP56/CHN chimeras. Furthermore, there were no chi, chi-like, topoisomerase II, or translin consensus sequences in the introns harboring the translocation breakpoints, nor could the number of topo I sites in EWS, RBP56, and CHN introns explain the uneven distribution of the breakpoints among EWS or CHN introns. Additional genetic events, such as nucleotide insertions, homologies at the junction, deletions, duplications, and inversions, were found to accompany the translocations, indicating that the chromosomal translocations do not require sequence-specific recombinases or extensive homology between the recombined sequences.
骨外黏液样软骨肉瘤（EMC）是一种软组织肿瘤，其细胞遗传学特征为易位t(9;22)(q22;q11 - 12)或t(9;17)(q22;q11)，分别产生EWS/CHN或RBP56/CHN融合基因。在本研究中，对18例EMC进行了细胞遗传学和分子水平的研究。在16个样本中检测到染色体畸变：13例涉及9q22和22q11 - 12，3例涉及9q22和17q11的重排。15例有EWS/CHN融合转录本，3例有RBP56/CHN转录本。最常见的EWS/CHN转录本（1型；10个肿瘤）涉及EWS外显子12与CHN外显子3的融合，第二常见的（5型；2例）是EWS外显子13与CHN外显子3的融合。在所有具有RBP56/CHN融合的肿瘤中，RBP56的外显子6与CHN的外显子3融合。通过基因组XL PCR和序列分析，14例病例的断点定位在EWS、RBP56和CHN基因中。在CHN中，12个断点位于内含子2，仅2个位于内含子1。在EWS中，断点发生在内含子7（1个断点）、12（8个断点）和13（1个断点），在RBP56中发生在内含子6。诸如Alu和LINE序列等重复元件在EWS/CHN和RBP56/CHN嵌合体的发生中似乎作用有限（如果有作用的话）。此外，在含有易位断点的内含子中没有chi、chi样、拓扑异构酶II或转座蛋白共有序列，EWS、RBP56和CHN内含子中的拓扑异构酶I位点数量也无法解释EWS或CHN内含子中断点的不均匀分布。发现伴随易位出现了其他遗传事件，如核苷酸插入、连接处的同源性、缺失、重复和倒位，这表明染色体易位不需要序列特异性重组酶或重组序列之间的广泛同源性。
