Tumorigenesis -: RAF/RAS oncogenes and mismatch-repair status
Tumorigenesis -: RAF/RAS oncogenes and mismatch-repair status
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DOI：
10.1038/418934a
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发表时间：
2002-08-29
期刊：
影响因子：
64.8
通讯作者：
Velculescu, VE
中科院分区：
文献类型：
--
作者：
Rajagopalan, H;Bardelli, A;Velculescu, VE
RAF家族的基因编码受RAS调控的激酶，并介导细胞对生长信号的反应。RAF基因BRAF的激活突变在高比例的黑色素瘤和一小部分其他癌症中被发现。在这里，我们证明了结直肠癌中的BRAF突变只发生在没有携带被称为KRAS的RAS基因突变的肿瘤中，并且BRAF突变与这些肿瘤修复DNA中不匹配的碱基的熟练程度有关。我们的结果不仅为BRAF和KRAS的突变在肿瘤发生中发挥同等作用的观点提供了遗传学支持，而且也强调了修复过程在建立支撑人类癌症的突变谱中的作用。
Genes of theRAFfamily encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in oneRAFgene,BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show thatBRAFmutations in colorectal cancers occur only in tumours that do not carry mutations in aRASgene known asKRAS, and thatBRAFmutation 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 inBRAFandKRASexert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.