Copy Number Alterations and Methylation in Ewing's Sarcoma.
Copy Number Alterations and Methylation in Ewing's Sarcoma.
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作者：
Jahromi MS;Jones KB;Schiffman JD
尤文氏肉瘤是影响儿童和年轻人的第二大常见骨恶性肿瘤。转移性或复发性疾病的预后尤其差。起源细胞尚不清楚，但EWS-FLI1融合癌蛋白存在于大多数病例中。对尤文氏肉瘤分子基础的了解进展缓慢。EWS-FLI1影响基因表达，但其他因素也必须起作用，如突变、基因拷贝数改变和启动子甲基化。本文深入探讨了尤文氏肉瘤的两个分子方面：拷贝数改变（CNAs）和甲基化。虽然CNAs一直在尤文氏肉瘤中被报道，但它们的临床意义一直是可变的，很可能是由于样本量小和肿瘤异质性。甲基化被认为在肿瘤发生和平衡核型癌症（如Ewing's）中很重要，但在先前的研究中只得到很少的关注。未来的CNA和甲基化研究将有助于了解这种疾病的分子基础。
Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs) and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease.