英国《自然》（Nature）杂志8月24日发表的一项研究结果显示，一种名为ALK的基因发生变异，会增加儿童患神经母细胞瘤的风险。
来自美国、意大利和比利时的研究人员介绍说，他们对20个家庭进行了研究，其中每个家庭有一名以上的儿童患神经母细胞瘤。研究发现，ALK基因发生特定变异后会持续处于活跃状态，从而促进细胞的增殖。细胞不受控制地增殖，通常是癌症发病的标志。
神经母细胞瘤是一种较为罕见的儿童癌症，它会损伤儿童的神经系统，儿童患上这种癌症的存活率仅有40%。
研究人员认为，新研究成果将有助于从遗传角度加深对儿童神经母细胞瘤的认识，同时也为开发诊断和治疗这种疾病的新方法提供了线索。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature，doi:10.1038/nature07261，Ya?l P. Mossé, John M. Maris
Identification of ALK as a major familial neuroblastoma predisposition gene
Yaël P. Mossé1, Marci Laudenslager1, Luca Longo2, Kristina A. Cole1, Andrew Wood1, Edward F. Attiyeh1, Michael J. Laquaglia1, Rachel Sennett1, Jill E. Lynch1, Patrizia Perri2,3, Geneviève Laureys4, Frank Speleman4, Cecilia Kim5, Cuiping Hou1,5, Hakon Hakonarson5,7, Ali Torkamani6, Nicholas J. Schork6, Garrett M. Brodeur1, Gian P. Tonini2, Eric Rappaport1, Marcella Devoto7,8 & John M. Maris1,9
Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23–24 using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high-risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild-type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy
