Department of Pediatrics, University of California Davis, MIND Institute, Sacramento, California.
RASopathies Network, Altadena, California.
Am J Med Genet A. 2018 Dec;176(12):2924-2929. doi: 10.1002/ajmg.a.40632. Epub 2018 Oct 10.
This report summarizes and highlights the fifth International RASopathies Symposium: When Development and Cancer Intersect, held in Orlando, Florida in July 2017. The RASopathies comprise a recognizable pattern of malformation syndromes that are caused by germ line mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway. Because of their common underlying pathogenetic etiology, there is significant overlap in their phenotypic features, which includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, gastrointestinal and ocular abnormalities, neurological and neurocognitive issues, and a predisposition to cancer. The RAS pathway is a well-known oncogenic pathway that is commonly found to be activated in somatic malignancies. As in somatic cancers, the RASopathies can be caused by various pathogenetic mechanisms that ultimately impact or alter the normal function and regulation of the MAPK pathway. As such, the RASopathies represent an excellent model of study to explore the intersection of the effects of dysregulation and its consequence in both development and oncogenesis.
本报告总结并重点介绍了 2017 年 7 月在佛罗里达州奥兰多举行的第五届国际 RAS 病综合征研讨会：发育与癌症的交汇点。RAS 病综合征由编码 RAS/丝裂原活化蛋白激酶（MAPK）途径组成部分的基因种系突变引起的可识别的畸形综合征模式组成。由于其共同的潜在发病机制病因，其表型特征存在显著重叠，包括颅面畸形、心脏、皮肤、肌肉骨骼、胃肠道和眼部异常、神经和神经认知问题，以及癌症易感性。RAS 途径是一种众所周知的致癌途径，在体细胞恶性肿瘤中常被发现被激活。与体细胞癌症一样，RAS 病综合征可由各种最终影响或改变 MAPK 途径正常功能和调节的发病机制引起。因此，RAS 病综合征代表了一个极好的研究模型，可探索发育和肿瘤发生过程中失调及其后果的交叉点。
