| GeneLibs

题目:: Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma.
作者:: Kridel(Robert),Meissner(Barbara),Rogic(Sanja),Boyle(Merrill),Telenius(Adele),Woolcock(Bruce),Gunawardana(Jay),Jenkins(Christopher),Cochrane(Chris),Ben-Neriah(Susana),Tan(King),Morin(Ryan D),Opat(Stephen),Sehn(Laurie H),Connors(Joseph M),Marra(Marco A),Weng(Andrew P),Steidl(Christian),Gascoyne(Randy D)
状态:: 发布时间2012-03-02 , 更新时间 2012-03-02
期刊:: Blood
摘要:: Mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma, is characterized by the hallmark translocation t(11;14)(q13;q32) and the resulting overexpression of cyclin D1 (CCND1). Our current knowledge of this disease encompasses frequent secondary cytogenetic aberrations and the recurrent mutation of a handful of genes, such as TP53, ATM, and CCND1. However, these findings insufficiently explain the biologic underpinnings of MCL. Here, we performed whole transcriptome sequencing on a discovery cohort of 18 primary tissue MCL samples and 2 cell lines. We found recurrent mutations in NOTCH1, a finding that we confirmed in an extension cohort of 108 clinical samples and 8 cell lines. In total, 12% of clinical samples and 20% of cell lines harbored somatic NOTCH1 coding sequence mutations that clustered in the PEST domain and predominantly consisted of truncating mutations or small frame-shifting indels. NOTCH1 mutations were associated with poor overall survival (P = .003). Furthermore, we showed that inhibition of the NOTCH pathway reduced proliferation and induced apoptosis in 2 MCL cell lines. In summary, we have identified recurrent NOTCH1 mutations that provide the preclinical rationale for therapeutic inhibition of the NOTCH pathway in a subset of patients with MCL.
语言:: eng
DOI:: 10.1182/blood-2011-11-391474

文献库文献相关信息

DataTable pData

联系方式

微信公众号

文献库 文献相关信息

DataTable pData

联系方式

微信公众号

文献库文献相关信息