Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor.
Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor.
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DOI：
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发表时间：
1994-06
期刊：
影响因子：
11.2
通讯作者：
M. Ladanyi;W. Gerald
中科院分区：
文献类型：
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作者：
M. Ladanyi;W. Gerald
促结缔组织增生性小圆细胞肿瘤(DSRCT)是一种新近发现的原始肉瘤类型，其特点是好发于年轻男性，临床表现具有侵袭性，广泛累及腹部浆膜，具有明显的促结缔组织增生和显著的分化、多系分化。以前的细胞遗传学病例报告发现了一种复发性易位，t(11；22)(p13；q12)。我们已经使用候选基因方法在五个DSRCT的小组中在分子水平上表征了这种易位。Southern印迹分析显示，在尤文氏肉瘤和透明细胞肉瘤中，位于22q12的两个EWS反复重排，并在其他肿瘤特异性易位中重排，以及与Wilms肿瘤的一个亚群有关的11p13基因WT1的重排。重组的EWS和WT1条带在多个酶切中的一致迁移表明基因组序列融合，可能是由于t(11；22)易位(p13；q12)。Northern blotting显示EWS和WT1转录本大小相同，表明存在嵌合信使RNA。使用EWS外显子7和WT1外显子8或9的逆转录聚合酶链式反应证实了这一点，发现了与EWS外显子7和WT1外显子8连接的单一聚合酶链式反应产物。因此，DSRCT是第三例涉及EWS基因的原始肉瘤，也是第一例肿瘤抑制基因WT1在特定肿瘤类型中的反复重排。EWS基因不同的易位配对可能是DSRCT、尤文氏肉瘤和透明细胞肉瘤生物学差异的原因，它们都是假定或确定的转录因子基因。
The desmoplastic small round cell tumor (DSRCT) is a recently recognized type of primitive sarcoma defined by a predilection for young males, aggressive clinical behavior, widespread abdominal serosal involvement, and a primitive histological appearance with prominent desmoplasia and striking divergent, multilineage differentiation. Previous cytogenetic case reports have identified a recurrent translocation, t(11;22) (p13;q12). We have characterized this translocation at the molecular level in a panel of five DSRCTs using a candidate gene approach. Southern blot analysis revealed recurrent rearrangement of both EWS, located at 22q12, and rearranged in other tumor-specific translocations in Ewing's sarcoma and clear cell sarcoma, and of WT1, the gene at 11p13 involved in a subset of Wilms' tumor. Consistent comigration of the rearranged EWS and WT1 bands in multiple enzyme digests indicated fusion of the genomic sequences, presumably due to the translocation t(11;22) (p13;q12). Northern blotting showed aberrant EWS and WT1 transcripts of the same size, suggesting the presence of a chimeric messenger RNA. This was confirmed by reverse transcriptase polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 or 9 primers, which revealed single polymerase chain reaction products consistent with a junction of EWS exon 7 to WT1 exon 8. DSRCT thus represents the third primitive sarcoma in which the EWS gene is involved and the first instance of recurrent rearrangement of a tumor suppressor gene, WT1, in a specific tumor type. The different translocation partners of the EWS gene, all of which are putative or definite transcription factor genes, may be responsible for the biological differences between DSRCT, Ewing's sarcoma, and clear cell sarcoma.