Somatic Activating KRAS Mutations in Arteriovenous Malformations of the Brain.

The New England Journal of Medicine
Sergey I NikolaevIvan Radovanovic

Abstract

Sporadic arteriovenous malformations of the brain, which are morphologically abnormal connections between arteries and veins in the brain vasculature, are a leading cause of hemorrhagic stroke in young adults and children. The genetic cause of this rare focal disorder is unknown. We analyzed tissue and blood samples from patients with arteriovenous malformations of the brain to detect somatic mutations. We performed exome DNA sequencing of tissue samples of arteriovenous malformations of the brain from 26 patients in the main study group and of paired blood samples from 17 of those patients. To confirm our findings, we performed droplet digital polymerase-chain-reaction (PCR) analysis of tissue samples from 39 patients in the main study group (21 with matching blood samples) and from 33 patients in an independent validation group. We interrogated the downstream signaling pathways, changes in gene expression, and cellular phenotype that were induced by activating KRAS mutations, which we had discovered in tissue samples. We detected somatic activating KRAS mutations in tissue samples from 45 of the 72 patients and in none of the 21 paired blood samples. In endothelial cell-enriched cultures derived from arteriovenous malformatio...Continue Reading

References

Aug 15, 2000·Neurosurgery·M F BermanW L Young
Oct 30, 2001·The Journal of Biological Chemistry·K N MeadowsK Pumiglia
Oct 25, 2002·Journal of Neurology, Neurosurgery, and Psychiatry·R Al-ShahiC P Warlow
Jan 28, 2004·Neurosurgery·Tomoki HashimotoWilliam L Young
Aug 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Patrick A MurphyRong A Wang
Jun 24, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·Patrick A MurphyRong A Wang
Oct 9, 2009·Brain : a Journal of Neurology·Qichuan ZhuGeKunlin Jin
Jul 16, 2010·The Biochemical Journal·Ana Cuadrado, Angel R Nebreda
Jan 21, 2012·Science Translational Medicine·Patrick A MurphyRong A Wang
Jan 19, 2013·Experimental Cell Research·Rui Benedito, Mats Hellström
May 21, 2014·Nature Reviews. Clinical Oncology·Yujie Zhao, Alex A Adjei
Dec 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Patrick A MurphyRong A Wang
Feb 3, 2015·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jason E Fish, Joshua D Wythe
Mar 3, 2015·American Journal of Human Genetics·Javier A CoutoArin K Greene
Sep 15, 2015·Plastic and Reconstructive Surgery·Javier A CoutoArin K Greene
Dec 8, 2015·American Journal of Human Genetics·Nisha LimayeMiikka Vikkula
Apr 9, 2016·American Journal of Human Genetics·Ugur M AyturkMatthew L Warman
Feb 14, 2017·American Journal of Human Genetics·Javier A CoutoArin K Greene
May 11, 2017·The New England Journal of Medicine·Michael S AnglesioIe-Ming Shih
Jul 1, 2017·Cell·Dhirendra K SimanshuFrank McCormick

❮ Previous
Next ❯

Citations

Dec 15, 2018·The Journal of Pathology·Daniel BaumhoerWolfgang Hartmann
Apr 20, 2019·Journal of Clinical Medicine·Roberto ChalelaJoaquim Gea
May 8, 2019·Scientific Reports·Elisa HytönenSeppo Ylä-Herttuala
Apr 3, 2019·International Angiology : a Journal of the International Union of Angiology·Stefano PaolacciMatteo Bertelli
Jun 28, 2019·Current Opinion in Pediatrics·Miguel Zúñiga-CastilloJoyce M C Teng
Jun 7, 2019·Journal of the American Heart Association·Ran HuoJizong Zhao
Aug 12, 2019·Journal of Neurointerventional Surgery·Xinghuan DingKun Wang
Nov 11, 2019·The Journal of Pathology·Carolina C GomesRicardo S Gomez
Mar 4, 2020·Journal of the European Academy of Dermatology and Venereology : JEADV·Marta Valdivielso-RamosIsabel Colmenero
Jan 1, 2020·PloS One·Jeremy A GossArin K Greene
May 14, 2020·Acta neurochirurgica·Patrik JärvelinJuhana Frösen
Jun 22, 2020·Clinical and Translational Medicine·Lorelei D ShoemakerSteven D Chang
Jun 20, 2020·Brain and Behavior·Jakša VukojevićPredrag Sikirić
Jul 3, 2020·Annals of Clinical and Translational Neurology·Ruojie HeJian Yu
Aug 28, 2020·Journal of Neurointerventional Surgery·Mingqi ZhangKun Wang
Jun 20, 2018·Neurosurgery·Robert M StarkeE Sander Connolly
Dec 7, 2018·Current Treatment Options in Pediatrics·Reema PadiaJonathan Perkins
Jun 11, 2019·Stroke; a Journal of Cerebral Circulation·Stéphanie LenckVitor Mendes Pereira
Oct 16, 2019·Mutagenesis·Congzhen QiaoXiaoxi Lin
Jan 12, 2020·Digestive Diseases and Sciences·Agnieszka PaziewskaJerzy Ostrowski
Jun 21, 2019·PLoS Computational Biology·Ruth NussinovHyunbum Jang
Mar 15, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Igor GiarrettaRoberto Pola
Apr 20, 2020·Acta neurochirurgica·Roosa WrightJuhana Frösen
Jun 3, 2020·Journal of Neuropathology and Experimental Neurology·Kwok Ling KamCraig Horbinski
Feb 7, 2020·Interventional Neuroradiology : Journal of Peritherapeutic Neuroradiology, Surgical Procedures and Related Neurosciences·Takahiro Ota, Masaki Komiyama
Aug 7, 2020·Circulation Research·Nagore I Marín-RamosFlorence M Hofman
Apr 20, 2018·The New England Journal of Medicine·Hiroyuki Morita, Issei Komuro
Jun 8, 2018·The British Journal of Dermatology·G MaX Lin
Oct 26, 2018·Genome Research·Geoffrey J MaherAnne Goriely
Mar 27, 2019·Annals of Clinical and Translational Neurology·Marco A StefaniJay P Mohr
Nov 17, 2019·International Journal of Molecular Sciences·Leandro Barbosa Do PradoHua Su
Jun 5, 2019·Scientific Reports·Astrid EijkelenboomHolger Rehmann
Apr 29, 2020·Nature Reviews. Cancer·Pau CastelFrank McCormick
Dec 5, 2019·Stroke; a Journal of Cerebral Circulation·Allard J HauerCatharina J M Klijn
Sep 5, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kaitlyn ZennerJames T Bennett
Oct 5, 2018·Frontiers in Oncology·Qingda MengMarkus Maeurer
Jun 13, 2019·The Journal of Pathology·Vivian LacDavid G Huntsman
Jul 31, 2019·CNS Neuroscience & Therapeutics·Sonali S ShaligramHua Su

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