Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.     

软件工程知识的获取

本书是由新加坡世界科技出版公司出版的《软件工程与知识工程丛书》的第14卷。未来的软件系统将分布在整个网络上，并具有专门从事不同活动的代理。每一个代理都具有不同程度上的自治。软件开发机构将会依靠这些代理，利用不同的程序开发过程来生产软件程序。本书从遗传编程的角度讨论了具体的不同之处。作者试图通过设计一个用于演化程序的软件工程环境系统（SWEEP），来使我们对于开发多代理、多过程的未来的洞察力变得更为具体。SWEEP系统使用遗传编程在软件的创建与修改中起了中心的作用。此外，还对度量学特别注意，探索了可通用性、程序肿胀和有效程序长度问题。