Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas.

Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies

AMP-Activated Protein Kinase: A Metabolic Stress Sensor in the Heart

International audienceAMP-activated protein kinase (AMPK) is a central cellular signaling hub that senses and responds to different kinds of stress, mainly those triggered by impaired cellular energy homeostasis. Since this is of major importance for the heart, the kinase plays important roles for cardiovascular function in human health and disease. Here, we review recent progress on the molecular structure and role of AMPK and summarize regulation and biological actions of the AMPK pathway, in particular those relevant for the heart. Activation of the kinase is involved in the myocardial response to ischemia, pressure overload, and heart failure. Pharmacological activation of AMPK may prove to be a useful therapeutic strategy in the treatment of these pathologies. (PDF) AMP-Activated Protein Kinase: A Metabolic Stress Sensor in the Heart. Available from: https://www.researchgate.net/publication/283756966_AMP-Activated_Protein_Kinase_A_Metabolic_Stress_Sensor_in_the_Heart [accessed Dec 10 2018]