期刊
THROMBOSIS RESEARCH
卷 164, 期 -, 页码 S136-S142出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2018.01.021
关键词
Tissue factor; Medulloblastoma; Glioblastoma; Single cell sequencing; Coagulome
资金
- Canadian Institutes for Health Research (CIHR Foundation grant) [MOP 102736, MOP 111119]
- Canadian Cancer Society Innovation to Impact (CCSRI)
- McGill Integrated Cancer Research Training Program (MICRTP)
- Tomlinson Program
- Piccoli 401 Bike Challenge Fund
- Michael Whitehead and Louise Penney Award
- Fonds de Recherche en Sante du Quebec (FRSQ)
Molecular profiling of human cancers revealed a startling diversity in disease-causing mechanisms superseding histological and anatomical commonalities. The emerging molecular subtypes and disease entities are often driven by distinct oncogenic pathways and their effectors, including those acting extracellularly on the vascular and coagulation systems. Indeed, several oncogenic mutations such as those affecting protein-coding genes (RAS, EGFR, PTEN, TP53) and non-coding RNA (microRNA) regulate multiple effectors of the coagulation system (coagulome), including tissue factor, protease activated receptors, dotting factors, mediators of platelet function and fibrinolysis. This is exemplified by differential coagulome profiles in the molecular subtypes of glioblastoma, medulloblastoma and other human tumours. There is mounting clinical evidence that the mutational status of cancer driver genes such as KRAS or IDH1 may influence the risk of venous thromboembolism in patients with colorectal, lung or brain cancers. Notably, single cell sequencing in glioblastoma revealed a remarkable intratumoural heterogeneity of cancer cell populations with regard to their individual coagulomes, suggesting a combinatorial and dynamic nature of the global pro-thrombotic phenotype. We suggest that the cellular complexity of specific cancers may define their mechanisms of interactions with the coagulation system, and the risks of thrombosis. Thus, more biologically-based, disease-specific and personalized approaches may be needed to diagnose and manage cancer-related thrombosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据