Ladanyi M, Gerald W
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer Res. 1994 Jun 1;54(11):2837-40.
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.
促结缔组织增生性小圆细胞肿瘤（DSRCT）是一种最近才被认识的原始肉瘤，其特点是好发于年轻男性，临床行为侵袭性强，广泛累及腹部浆膜，具有原始的组织学表现，伴有明显的促结缔组织增生以及显著的不同方向的多谱系分化。既往细胞遗传学病例报告已鉴定出一种复发性易位，即t(11;22)(p13;q12)。我们采用候选基因方法在一组5例DSRCT中对这种易位进行了分子水平的特征分析。Southern印迹分析显示，位于22q12的EWS以及在尤因肉瘤和透明细胞肉瘤的其他肿瘤特异性易位中发生重排的EWS，与位于11p13的WT1基因（该基因参与一部分肾母细胞瘤）均发生了复发性重排。在多种酶切消化中，重排的EWS和WT1条带的一致共迁移表明基因组序列发生了融合，推测是由于t(11;22)(p13;q12)易位所致。Northern印迹显示大小相同的异常EWS和WT1转录本，提示存在嵌合信使RNA。这通过使用EWS外显子7引物和WT1外显子8或9引物进行逆转录聚合酶链反应得到证实，该反应揭示了单一的聚合酶链反应产物，与EWS外显子7与WT1外显子8的连接一致。因此，DSRCT是EWS基因参与的第三种原始肉瘤，也是特定肿瘤类型中肿瘤抑制基因WT1复发性重排的首例。EWS基因的不同易位伙伴，所有这些伙伴均为推定的或确定的转录因子基因，可能是DSRCT、尤因肉瘤和透明细胞肉瘤之间生物学差异的原因。
