Futreal P A, Wooster R, Stratton M R
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Cold Spring Harb Symp Quant Biol. 2005;70:43-9. doi: 10.1101/sqb.2005.70.015.
All cancers arise due to the accumulation of mutations in critical target genes that, when altered, give rise to selective advantage in the cell and its progeny that harbor them. Knowledge of these mutations is key in understanding the biology of cancer initiation and progression, as well as the development of more targeted therapeutic strategies. We have undertaken a systematic screen of all annotated protein kinases in the human genome for mutations in a series of cancers including breast, non-small-cell lung, and testicular cancer. Our results show a wide diversity in mutation prevalence within and between tumor types. We have identified a mutator phenotype in human breast previously undescribed. The results presented from sequencing the same 1.3 million base pairs through several tumor types suggest that most of the observed mutations are likely to be passenger events rather than causally implicated in oncogenesis. However, this work does provide evidence for the likely existence of multiple, infrequently mutated kinases.
所有癌症都是由于关键靶基因中突变的积累所致，这些基因一旦发生改变，就会在携带它们的细胞及其子代中产生选择性优势。了解这些突变对于理解癌症发生和发展的生物学机制以及开发更具针对性的治疗策略至关重要。我们对人类基因组中所有注释的蛋白激酶进行了系统筛选，以寻找包括乳腺癌、非小细胞肺癌和睾丸癌在内的一系列癌症中的突变。我们的结果显示，肿瘤类型内部和之间的突变发生率存在广泛差异。我们在人类乳腺癌中发现了一种以前未描述过的突变表型。通过对几种肿瘤类型的相同130万个碱基对进行测序得出的结果表明，大多数观察到的突变可能是过客事件，而非致癌过程中的因果相关因素。然而，这项工作确实为可能存在多种罕见突变激酶提供了证据。
