Chromosome Instability Accounts for Reverse Metastatic Outcomes of Pediatric and Adult Synovial Sarcomas
Chromosome Instability Accounts for Reverse Metastatic Outcomes of Pediatric and Adult Synovial Sarcomas
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DOI：
10.1200/jco.2012.46.0147
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发表时间：
2013-02-10
影响因子：
45.3
通讯作者：
Chibon, Frederic
中科院分区：
文献类型：
--
作者：
Lagarde, Pauline;Przybyl, Joanna;Chibon, Frederic
滑膜肉瘤（Synovial sarcoma，SS）好发于儿童和成人，但转移性疾病在成人中更为常见。尽管t（X; 18）易位在SS肿瘤发生中的重要性已得到充分证实，但SS转移的遗传基础仍知之甚少。我们最近报道了表达（CINSARC;肉瘤的复杂性指数）和基因组指数与肉瘤和胃肠道间质瘤中染色体完整性相关的预后特征。在这里，我们调查这些签名是否也可以预测结果在SS.Patients和MethodsOne百例原发性未经治疗的SS肿瘤的患者被选为表达和基因组分析的训练/validationapproach.ResultsCINSARC和基因组指数有很强的独立和验证的预后价值（P < .001）。通过比较有或没有转移的肿瘤的表达谱，确定了CINSARC签名共有的14个基因，并且两个排名最高的基因KIF 14和CDCA 2在独立队列中被验证为预后标志物。比较成人与儿童SS的基因组图谱，我们发现，转移与基因组的复杂性在这两种情况下，成人基因组更频繁地重排。因此，儿科患者的基因组分布均匀，不发展metastasis. ConclusionMetastasisdevelopment在SS是强烈相关的染色体的复杂性，和CINSARC和基因组指数验证独立的预后因素。成人和儿童之间转移频率的差异与基因组不稳定性有关，这在成人中更常见。考虑到福尔马林固定样本的基因组分析已用于病理学，基因组指数可能是最佳的总体生物标志物，显然也是最具临床相关性的。J Clin Oncol 31：608-615. (C)2013年美国临床肿瘤学会
PurposeSynovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X; 18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS.Patients and MethodsOne hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach.ResultsCINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult versus pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis.ConclusionMetastasis development in SS is strongly associated with chromosome complexity, and CINSARC and Genomic Index are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology. J Clin Oncol 31:608-615. (C) 2013 by American Society of Clinical Oncology