EWS-FL11 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma
EWS-FL11 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma
复制标题
DOI：
10.1200/jco.1998.16.4.1248
复制
发表时间：
1998-04-01
影响因子：
45.3
通讯作者：
Ladanyi, M
中科院分区：
文献类型：
--
作者：
de Alava, E;Kawai, A;Ladanyi, M
目的：由于t（11;22）（q24;q12）易位，超过90%的尤文肉瘤（ES）含有EWS和FLI 1基因的融合。在分子水平上，EWS-FLI 1重排表现出很大的多样性。EWS和FLI 1外显子的多种不同组合编码符合读框的融合转录物，并导致嵌合蛋白的长度和组成的差异，其作为致癌异常转录因子发挥作用。在最常见的融合类型（1型）中，EWS外显子7与FLI 1的外显子6符合读框。这些融合转录物的分子异质性可能具有功能和临床意义。我们对112例ES患者进行了临床和病理分析，其中通过逆转录聚合酶链反应（RT-PCR）鉴定了EWS-FLI 1融合转录本，在99例接受根治性治疗的患者中获得了充分的治疗和随访VP数据。这99例患者的中位随访时间为26个月（范围：1至140个月）。单变量和多变量生存分析，包括其他预后因素，如年龄，肿瘤的位置，大小，和stage.Results：在99例适合生存分析，64例患者的肿瘤中包含1型融合，35例患者中包含不太常见的融合类型，在介绍阶段是本地化的74例患者和25转移。转移（相对风险[RR] = 2.6; P = .008），1型EWS-FLI 1融合（RR = 0.37; P = 0.014）分别是影响总生存率的独立负性和正性预后因素。在74例局限性肿瘤患者中，1型EWS-FLI 1融合也是总生存率的显著正性预测因子结论：EWS-FLI 1融合基因型与ES的发生密切相关，与肿瘤部位、分期、大小无关。需要进一步的研究来阐明这种现象的生物学基础。(C)1998年，美国临床肿瘤学会。
Purpose: More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor, In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1, As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance.Patients and Methods: We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR), Adequate treatment and follow-vp data were available in 99 patients treated with curative intent. Median follow-up in these 99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate survival analyses were performed that included other prognostic factors, such as age, tumor location, size, and stage.Results: Among the 99 patients suitable for survival analysis, the tumors in 64 patients contained the type 1 fusion and in 35 patients contained less common fusion types, Stage at presentation was localized in 74 patients and metastatic in 25. Metastases (relative risk [RR] = 2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014)were, respectively, independent negative and positive prognostic factors for overall survival by multivariate analysis, Among 74 patients with localized tumors, the type 1 EWS-FLI1 fusion was also a significant positive predictor of overall survival (RR = 0.32; P = .034) by multivariate analysis.Conclusion: EWS-FLI1 fusion type appears to be prognostically relevant in ES, independent of tumor site, stage, and size. Further studies are needed to clarify the biologic basis of this phenomenon. (C) 1998 by American Society of Clinical Oncology.