The consensus coding sequences of human breast and colorectal cancers
The consensus coding sequences of human breast and colorectal cancers
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DOI：
10.1126/science.1133427
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发表时间：
2006-10-13
期刊：
影响因子：
56.9
通讯作者：
Velculescu, Victor E.
中科院分区：
文献类型：
--
作者：
Sjoeblom, Tobias;Jones, Sian;Velculescu, Victor E.
人类基因组序列的阐明使得以前所未有的细节识别癌症中的遗传改变成为可能。为了开始对这种改变进行系统分析，我们确定了两种常见肿瘤类型中注释良好的人类蛋白质编码基因的序列。对11例乳腺癌和11例结直肠癌的13023个基因的分析显示，单个肿瘤平均积累了90个类似的突变基因，但其中只有一小部分参与了肿瘤的形成过程。使用严格的标准来描述这个子集，我们确定了189个基因（平均每个肿瘤11个）显著频率突变。这些基因中的绝大多数在肿瘤中不被遗传改变，预计会影响广泛的细胞功能，包括转录、粘附和侵袭。这些数据定义了两种人类癌症类型的遗传格局，为诊断和治疗干预提供了新的靶点，并为肿瘤生物学的基础研究开辟了丰富的途径。
The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of similar to 90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes ( average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.