Ozaki T, Paulussen M, Poremba C, Brinkschmidt C, Rerin J, Ahrens S, Hoffmann C, Hillmann A, Wai D, Schaefer K L, Boecker W, Juergens H, Winkelmann W, Dockhorn-Dworniczak B
Department of Orthopaedics, Westfälische Wilhelms-University, Domagkstrasse 17, 48149 Münster, Germany.
Genes Chromosomes Cancer. 2001 Oct;32(2):164-71. doi: 10.1002/gcc.1178.
Ewing tumors are characterized by reciprocal translocations involving the EWS gene on 22q12 fused to ETS transcription-factor family members. Little is known about further aberrations contributing to tumor development and progression. Sixty-two frozen tumors with known EWS rearrangements (52 primary tumors, 10 relapses) of ET patients registered in the EICESS protocol were analyzed by comparative genomic hybridization (CGH). The median number of changes in 52 primary and 10 relapsed cases was 2.5 and 5.0 per tumor (P = 0.153). Frequent abnormalities included gains of chromosomes 8, 12, 20, and 1q and losses of 16q and 19q. Neither number nor type of aberration was associated with histology, tumor size, disease stage, tumor localization, or histologic tumor response to chemotherapy. Among the 52 primary tumors, 26 with Type I fusion (EWS exon 7 to FLI1 exon 6) and 26 with other fusion types had a median of 2.0 and 3.0 aberrations per tumor, respectively (P = 0.031). Combinations of gains of chromosomes 8 and 12, gains of chromosome 20, and either gains of 8q or 18q and losses of 16q and 17p frequently occurred. The cumulative overall survival (OAS) was different between 35 patients with <5 aberrations and 13 patients with > or =5 aberrations (P = 0.009). Univariate analysis showed that patients with gains of 1q, 2q, 12, and 20 or losses of 16q and 17p had significantly lower OAS than those without aberrations. By multivariate analysis, loss of 16q (relative risk [RR] = 5.3; P = 0.0006) was an independent prognostic factor.
尤因肉瘤的特征是22号染色体长臂12区的EWS基因与ETS转录因子家族成员发生相互易位。对于导致肿瘤发生和进展的其他畸变了解甚少。通过比较基因组杂交（CGH）分析了62例登记在EICESS方案中的尤因肉瘤患者的冷冻肿瘤，这些肿瘤具有已知的EWS重排（52例原发性肿瘤，10例复发肿瘤）。52例原发性肿瘤和10例复发病例中，每个肿瘤变化的中位数分别为2.5和5.0（P = 0.153）。常见的异常包括8号、12号、20号染色体和1号染色体长臂的增加以及16号染色体长臂和19号染色体长臂的缺失。畸变的数量和类型均与组织学、肿瘤大小、疾病分期、肿瘤定位或肿瘤对化疗的组织学反应无关。在52例原发性肿瘤中，26例为I型融合（EWS第7外显子至FLI1第6外显子），26例为其他融合类型，每个肿瘤的畸变中位数分别为2.0和3.0（P = 0.031）。8号和12号染色体增加、20号染色体增加以及8号染色体长臂或18号染色体长臂增加与16号染色体长臂和17号染色体短臂缺失的组合经常出现。35例畸变<5个的患者与13例畸变≥5个的患者的累积总生存率（OAS）不同（P = 0.009）。单因素分析显示，1号染色体长臂、2号染色体长臂、12号和20号染色体增加或16号染色体长臂和17号染色体短臂缺失的患者的OAS显著低于无畸变的患者。多因素分析显示，16号染色体长臂缺失（相对风险[RR]=5.3；P = 0.0006）是一个独立的预后因素。
