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【medical-news】神经母细胞瘤突变基因ALK被发现 有
儿童肿瘤可望出现新疗法
Researchers have identified genetic mutations underlying a childhood cancer of the nervous system called neuroblastoma. The mutations are the primary drivers behind the inherited form of the disease, and are also strongly associated with a non-inherited form that carries a particularly high risk of death.
科学家们最近发现了一个和神经母细胞瘤，一种儿童神经系统肿瘤密切相关的基因变异。这种变异是遗传性神经母细胞瘤发病的最根本原因，和死亡率很高的非遗传性神经母细胞瘤也密切相关。
The mutations lie in a gene called anaplastic lymphoma kinase (ALK ) that has been associated with an increased risk of other cancers, including a form of lung cancer. Several companies are developing drugs that inhibit the ALK protein, as a potential means of treating these cancers. The new results, says study author Yael Mossé of the Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, suggest that such inhibitors could provide a therapy for neuroblastoma as neuroblastoma is the most common form of cancer in infants, accounting for 15% of childhood cancer deaths. The disease has been mysterious not only in its origins but also in how it progresses: some children with neuroblastoma recover spontaneously, whereas others have a highly invasive form of the disease that does not respond to treatment. For children in the latter category, the cancer is often fatal.
这种突变位于间变性淋巴瘤激酶基因上，ALK和许多其他肿瘤，包括肺癌的一种类型的发病密切相关。许多公司因此致力于开发新药抑制ALK蛋白的活性来治疗上述肿瘤。宾州大学医学院，费城儿童医院的Yael Mossé，同时也是这项研究的作者认为，ALK蛋白的抑制剂将为神经母细胞瘤的治疗带来一种新的疗法。神经母细胞瘤是婴儿最常见的一种肿瘤，占了儿童癌症相关性死亡的15%。对于神经母细胞瘤的起源和疾病进展，目前都还不清楚，有些患儿会出现自愈，但有些患儿的肿瘤却呈现高度恶性，化疗无效，对于后一种患儿，这种肿瘤是致命的。
Mutation hunting
About 1% of the time, neuroblastoma is inherited; the remaining cases arise spontaneously. Mossé and her colleagues tracked down the ALK gene by first studying families with a history of the disease. They scanned the genome of nine families that had an average of four members with neuroblastoma per family, and found a region on chromosome 2 that was associated with the cancer.
突变追踪
1%的神经母细胞瘤是遗传性的，其他的则是自发性的。Mossé和她的同事正是在研究神经母细胞瘤家系时，发现ALK基因在此疾病中具有重要地位。这个研究小组一共研究了9个神经母细胞瘤家系，平均每个家系有4名患者，他们发现，其2号染色体上有一个区域和神经母细胞瘤密切相关。
There were 104 genes in that region, but two stood out as genes that had previously been shown to be linked to some cancers: ALK and another gene associated with cancer called MYCN . The researchers sequenced both genes and found mutations in ALK . The results were presented this week at the meeting of the American Association for Cancer Research in San Diego, California.
这个区域中一共包含了140个基因，其中，ALK和另一个基因已经被发现和肿瘤有关。研究人员将这两个基因分别测序，在ALK上发现了变异。以上研究成果将在本周于圣地亚哥举行的的美国癌症研究会上公布。
The researchers then turned their attention to the non-inherited form of the disease. They looked for variations in the number of copies of the ALK gene in 491 neuroblastoma tumour samples, and found that cells in 112 of the samples contained extra copies of ALK . Furthermore, increased copies of ALK were strongly linked to the invasive, high-risk form of the disease.
研究者又对非遗传性神经母细胞瘤进行了研究。他们一共检测了491个神经母细胞瘤瘤患儿的ALK基因拷贝数，发现112个患儿基因拷贝数增多，而且 ，基因拷贝数增加和肿瘤的高风险性、高侵袭性密切相关。
That finding is particularly important, says Susan Cohn of the University of Chicago, a paediatric oncologist who has studied neuroblastoma. "It is this subset of patients that desperately need more effective therapy," she says. Cohn says it is likely that the ALK protein will provide a clinically useful target for treating neuroblastoma, but notes that further studies are needed to determine what the protein actually does. In addition, the results may yield a genetic test for the disease that could be used for personalized medicine.
芝加哥大学的儿童肿瘤学家Susan Cohn认为，这一发现具有重要意义：她说“这部分病人特别需要有效的治疗。”
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作者:admin@医学,生命科学 2010-11-08 17:11
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