Denayer E, de Ravel Th, Legius E
Department of Human Genetics, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
J Med Genet. 2008 Nov;45(11):695-703. doi: 10.1136/jmg.2007.055772. Epub 2008 Jun 11.
RAS proteins play key roles in normal cell growth, malignant transformation and learning and memory. Somatic mutations in RAS genes and several of their upstream and downstream molecules result in different human malignancies. In recent years germline mutations in genes coding for components of the RAS signalling cascade have been recognised in a group of phenotypically overlapping disorders, referred to as the neuro-cardio-facial-cutaneous syndromes. These present with variable degrees of psychomotor delay, cardiac abnormalities, facial dysmorphism, short stature, skin defects and increased cancer risk. These findings point to important roles for this evolutionary conserved pathway not only in oncogenesis, but also in cognition, growth and development. Other constitutional disorders caused by mutated RAS pathway genes point to involvement of the RAS-MAPK pathway in immune modulation and vascular development.
RAS蛋白在正常细胞生长、恶性转化以及学习和记忆过程中发挥着关键作用。RAS基因及其一些上游和下游分子的体细胞突变会导致不同的人类恶性肿瘤。近年来，在一组表型重叠的疾病（称为神经-心脏-面部-皮肤综合征）中，已识别出编码RAS信号级联反应成分的基因中的种系突变。这些疾病表现出不同程度的精神运动发育迟缓、心脏异常、面部畸形、身材矮小、皮肤缺陷以及癌症风险增加。这些发现表明，这一进化保守通路不仅在肿瘤发生中起重要作用，而且在认知、生长和发育中也起重要作用。由RAS通路基因突变引起的其他先天性疾病表明RAS-MAPK通路参与免疫调节和血管发育。
