Knezevich S R, Hendson G, Mathers J A, Carpenter B, Lopez-Terrada D, Brown K L, Sorensen P H
Department of Pathology, BC's Children's Hospital, Vancouver, Canada.
Hum Pathol. 1998 Mar;29(3):289-94. doi: 10.1016/s0046-8177(98)90049-1.
Ewing sarcoma and other peripheral primitive neuroectodermal tumors (pPNETs) display limited neural differentiation and are thought to have a neural crest origin Greater than 95% of these tumors share common t(11;22)(q24;q12) ort(21;22)(q22;q12) chromosomal translocations leading to ES/FLI1 or EWS/ERG gene fusions, respectively. The resulting chimeric oncoproteins seem to function as aberrant transcription factors. However, whether these molecules contribute to the limited neural differentiation observed in pPNETs or actually inhibit differentiation remains unclear. We report a Ewing sarcoma case from the forearm of a 10-year-old girl which expressed EWS/FLI1 fusion transcripts. The tumor was treated with surgery, chemotherapy, and local radiation, but residual tumor was detected within a year as a well-differentiated peripheral neural tumor lacking detectable EWS/FLI1 expression. Further studies suggested that the primary and residual tumors were clonally related. This association between apparent therapy-induced differentiation in Ewing sarcoma and absence of detectable fusion transcripts in the residual tumor provides presumptive evidence that EWS/FLI1 expression may inhibit differentiation in tumour cells.
尤因肉瘤和其他外周原始神经外胚层肿瘤（pPNETs）显示出有限的神经分化，被认为起源于神经嵴。超过95%的这些肿瘤具有常见的t(11;22)(q24;q12)或t(21;22)(q22;q12)染色体易位，分别导致ES/FLI1或EWS/ERG基因融合。产生的嵌合癌蛋白似乎起着异常转录因子的作用。然而，这些分子是否导致pPNETs中观察到的有限神经分化或实际上抑制分化仍不清楚。我们报告了一例来自一名10岁女孩前臂的尤因肉瘤病例，该病例表达EWS/FLI1融合转录本。该肿瘤接受了手术、化疗和局部放疗，但在一年内检测到残留肿瘤，为一个缺乏可检测到的EWS/FLI1表达的高分化外周神经肿瘤。进一步研究表明，原发肿瘤和残留肿瘤是克隆相关的。尤因肉瘤中明显的治疗诱导分化与残留肿瘤中缺乏可检测到的融合转录本之间的这种关联提供了推测性证据，即EWS/FLI1表达可能抑制肿瘤细胞的分化。
