Kaneko Y, Kobayashi H, Handa M, Satake N, Maseki N
Department of Cancer Chemotherapy, Saitama Cancer Center Hospital, Japan.
Genes Chromosomes Cancer. 1997 Mar;18(3):228-31.
The EWS gene is fused in Ewing sarcoma-like tumors by a chromosomal translocation to one of the four ETS-family genes: FLI1, ERG, ETV1, and E1AF. The orientation of EWS and FLI1 on chromosomes 22 and 11, respectively, is 5' centromeric and 3' telomeric, whereas that of ERG on chromosome 21 is the reverse. Although 10% of Ewing-family tumors express the EWS-ERG fusion transcript, there have been no reports on tumors with t(21;22)(q22;q12) identified by banding cytogenetics. We found the karyotype 50, XY, +8, +8, +12, +mar in all metaphase cells from a tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis performed on the tumor and direct sequencing of the products identified the EWS-ERG fusion transcript. Subsequent two-color fluorescence in situ hybridization (FISH) analysis with EWS and ERG clones showed the fused signals on the der(21) chromosome, but no ERG signals on the chromosome 22 homologs. Thus, our RT-PCR and FISH analyses indicated that the chromosome 22 fragment containing the 5' portion of EWS had been inverted and inserted into chromosome 21 and had fused to the 3' portion of ERG. This subtle chromosome aberration could not be identified by routine cytogenetics. A chromosomal inversion/insertion has also been described in acute leukemia with the MLL-AF10 fusion gene, and this may be a common pathway for producing fusion of reverse-oriented genes in leukemias and solid tumors.
EWS基因在尤因肉瘤样肿瘤中通过染色体易位与四个ETS家族基因之一融合：FLI1、ERG、ETV1和E1AF。EWS和FLI1在22号和11号染色体上的方向分别是5'着丝粒和3'端粒，而ERG在21号染色体上的方向则相反。虽然10%的尤因家族肿瘤表达EWS-ERG融合转录本，但尚未有关于通过染色体显带细胞遗传学鉴定出t(21;22)(q22;q12)肿瘤的报道。我们在一个肿瘤的所有中期细胞中发现核型为50, XY, +8, +8, +12, +mar。对该肿瘤进行逆转录聚合酶链反应（RT-PCR）分析并对产物进行直接测序，鉴定出EWS-ERG融合转录本。随后用EWS和ERG克隆进行双色荧光原位杂交（FISH）分析，结果显示在der(21)染色体上有融合信号，但在22号染色体同源物上没有ERG信号。因此，我们的RT-PCR和FISH分析表明，包含EWS 5'部分的22号染色体片段发生了倒位并插入到21号染色体中，并与ERG的3'部分融合。这种细微的染色体畸变通过常规细胞遗传学无法识别。在伴有MLL-AF10融合基因的急性白血病中也描述了一种染色体倒位/插入，这可能是白血病和实体瘤中产生反向定向基因融合的常见途径。
