Genome wide analysis of imprinting gene in pediatric solid tumor

99例Ewing肉瘤ALK突变分析发现4个新的错义突变。功能分析显示ALK在裸鼠体内具有自磷酸化和肿瘤形成的作用。在神经母细胞瘤细胞系中观察到ALK异常激活的另一种机制，其中具有截断的细胞外结构域的短形式ALK蛋白过度表达。alk转导的NIH3T3细胞在软琼脂中表现出增加的集落形成能力和在裸鼠中的致瘤性。55例横纹肌肉瘤（rhabdomyosarcoma， RMS）样本的SNP阵列分析表明，胚胎横纹肌肉瘤具有高倍性的特征，与染色体2、8和12的增加显著相关，而大多数肺泡横纹肌肉瘤病例表现出近二倍体的拷贝数谱。15q杂合性缺失在肺泡RMS中被高度检测到。13q的增加与胚胎RMS患者的良好预后显著相关。

Analysis of ALK mutation in 99 cases with Ewing sarcoma revealed 4 novel missense mutations. Functional analysis of ALK showed autophosphorylation and tumor formation in nude mouse. Another mechanism of aberrant ALK activation was observed in a neuroblastoma cell line, in which a short-form ALK protein having a truncated extracellular domain is overexpressed. ALK-transduced NIH3T3 cells exhibited increased colony-forming capacity in soft agar and tumorigenicity in nude mice. SNP array analyses of 55 rhabdomyosarcoma(RMS) samples showed that the embrynal RMS was characterized by hyperploidy, significantly associated with gains of chromosomes 2, 8 and 12, whereas the majority of alveolar RMS cases exhibited near-diploid copy number profiles. Loss of heterozygosity of 15q was highly detected in alveolar RMS. Gain of 13q was significantly associated with good patient outcome in embryonal RMS.