Rajagopalan Harith, Bardelli Alberto, Lengauer Christoph, Kinzler Kenneth W, Vogelstein Bert, Velculescu Victor E
Sidney Kimmel Comprehensive Cancer Centre, Howard Hughes Medical Institution and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Nature. 2002 Aug 29;418(6901):934. doi: 10.1038/418934a.
Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.
RAF家族基因编码受Ras调节并介导细胞对生长信号作出反应的激酶。在高比例的黑色素瘤以及一小部分其他癌症中发现了一个RAF基因（BRAF）的激活突变。我们在此表明，结直肠癌中的BRAF突变仅发生在不携带名为KRAS的RAS基因突变的肿瘤中，并且BRAF突变与这些肿瘤修复DNA错配碱基的能力有关。我们的结果不仅为BRAF和KRAS突变在肿瘤发生中发挥同等作用这一观点提供了遗传学支持，还强调了修复过程在建立构成人类癌症基础的突变谱方面的作用。
