Boddicker Rebecca L, Razidlo Gina L, Feldman Andrew L
a Department of Laboratory Medicine and Pathology , Mayo Clinic , Rochester , MN , USA.
b Center for Basic Research in Digestive Diseases, Division of Gastroenterology & Hepatology, Mayo Clinic , Rochester , MN , USA.
Small GTPases. 2019 Jan;10(1):33-39. doi: 10.1080/21541248.2016.1263718. Epub 2017 Jan 6.
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy. These mutations include activating mutations and gene fusions involving the guanine nucleotide exchange factor, , as well as activating and dominant negative mutations in the GTPases and , respectively. In addition to mutations directly affecting the GTPase pathway, TCR signaling mutations indirectly affecting Ras- and Rho-family GTPases involving genes such as , and are also reviewed.
外周T细胞淋巴瘤（PTCL）是罕见的异质性肿瘤，对标准治疗反应不佳且可用的靶向治疗很少。在T细胞受体（TCR）信号通路中直接或间接影响Ras和Rho家族GTP酶的突变的鉴定是PTCL各亚型中一个新出现的主题。本综述总结了GTP酶在TCR信号传导中的作用，并强调了PTCL中该信号通路中的突变情况。特别关注了这些突变的功能影响和靶向治疗的机会。这些突变包括涉及鸟嘌呤核苷酸交换因子的激活突变和基因融合，以及分别在GTP酶 和 中的激活突变和显性负性突变。除了直接影响GTP酶途径的突变外，还综述了间接影响Ras和Rho家族GTP酶的TCR信号突变，这些突变涉及 、 和 等基因。
