High-throughput oncogene mutation profiling in human cancer
High-throughput oncogene mutation profiling in human cancer
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DOI：
10.1038/ng1975
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发表时间：
2007-03-01
期刊：
影响因子：
30.8
通讯作者：
Garraway, Levi A.
中科院分区：
文献类型：
--
作者：
Thomas, Roman K.;Baker, Alissa C.;Garraway, Levi A.
正在进行系统性的努力，以破译与肿瘤发生和进展相关的遗传变化（1，2）。然而，这种信息的广泛临床应用受到无法以足够的灵敏度和可扩展性识别人类肿瘤谱中的关键遗传事件的阻碍。在这里，我们采用高通量基因分型来查询1,000个人类肿瘤样本中的238个已知癌基因突变。这种方法建立了跨越17种癌症类型的稳健突变分布。在分析的17个癌基因中，我们发现14个至少发生了一次突变，298个（30%）样本至少发生了一次突变。此外，我们在几种肿瘤类型中发现了以前未被识别的癌基因突变，并观察到意外高数量的共同发生的突变。这些结果为肿瘤遗传学提供了一个新的维度，其中涉及多个癌症基因的突变可以同时和“真实的时间”进行询问，以指导癌症分类和合理的治疗干预。
Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression(1,2). However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.