Panagopoulos I, Mertens F, Isaksson M, Mandahl N
Department of Clinical Genetics, Lund University Hospital, Lund, S-221 85, Sweden.
Biochem Biophys Res Commun. 2000 Dec 29;279(3):838-45. doi: 10.1006/bbrc.2000.4026.
The cytogenetic hallmark of myxoid liposarcoma is the chromosomal aberration t(12;16)(q13;p11), which is pathognomonic for this tumor type. The translocation results in the hybrid gene FUS/CHOP, where the central and C-terminal parts of FUS, coding for the RNA binding domain and the RGG triplet motif, are replaced by the full length CHOP protein. Thus, CHOP is under the control of the FUS promoter and the FUS/CHOP chimera contains the 5'-terminal part of FUS which provides a transcriptional activation function. Although different structural variations of the FUS/CHOP chimeric transcript have been reported, none of them contains the parts of FUS encoding the RNA binding properties. An explanation is the location of the genomic breakpoint in FUS, which frequently occurs in the region spanning exon 5 to intron 8. We describe here a case of myxoid liposarcoma containing two novel FUS/CHOP chimeric transcripts and with the breakpoint occurring in intron 14 of FUS. Reverse transcription-polymerase chain reaction, using FUS forward and CHOP reverse primers, amplified strongly a 2.1-kbp DNA fragment and weakly a 0.9-kbp DNA fragment. Direct sequencing showed that in the 2.1-kbp transcript nt 1474, which corresponds to the third nucleotide of exon 14 of FUS, was in-frame fused to exon 2 of CHOP. In the 0.9-kbp DNA fragment, exon 3 of FUS was in-frame fused to exon 2 of CHOP. Genomic analyses revealed that the breaks were located at the end of exon 14/beginning of intron 14 of FUS and in intron 1 of CHOP and that microdeletions had occurred in the close vicinity of the breakpoints.
黏液样脂肪肉瘤的细胞遗传学特征是染色体畸变t(12;16)(q13;p11)，这是该肿瘤类型的特征性表现。这种易位导致融合基因FUS/CHOP的形成，其中FUS编码RNA结合结构域和RGG三联体基序的中央和C末端部分被全长CHOP蛋白取代。因此，CHOP受FUS启动子的控制，FUS/CHOP嵌合体包含FUS的5'-末端部分，该部分提供转录激活功能。尽管已经报道了FUS/CHOP嵌合转录本的不同结构变异，但它们均不包含编码RNA结合特性的FUS部分。一种解释是FUS中基因组断点的位置经常出现在跨越外显子5至内含子8的区域。我们在此描述了一例黏液样脂肪肉瘤，其包含两种新型FUS/CHOP嵌合转录本，断点发生在FUS的内含子14中。使用FUS正向引物和CHOP反向引物进行逆转录-聚合酶链反应，强烈扩增出一个2.1-kbp的DNA片段，微弱扩增出一个0.9-kbp的DNA片段。直接测序显示，在2.1-kbp转录本中，对应于FUS外显子14第三个核苷酸的nt 1474与CHOP的外显子2框内融合。在0.9-kbp DNA片段中，FUS的外显子3与CHOP的外显子2框内融合。基因组分析显示，断点位于FUS外显子14的末端/内含子14的起始处以及CHOP内含子1中，并且在断点附近发生了微缺失。
