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1 February 2020
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Amplification of EGFR is common in cancer cells and often occurs on extrachromosomal DNA Clarke and colleagues discovered previously unknown mechanisms that modulate this EGFR copy-number gain Specifically, methylation of histone 3 at lysine residue 9 or 27 (H3K9Me or H3K27Me) decreased EGFR amplification and expression In contrast, H3K4Me enhanced EGFR amplification Interestingly, exposure to hypoxic conditions or treatment with EGFR's preferred ligand, EGF, both promoted EGFR amplification In both cases, this effect was mediated by the H3K9/36 demethylase KDM4A Further investigation of these newly uncovered pathways may lead to the identification of new drug targets or mechanisms of resistance to EGFR inhibitors For details, please see the article by Clarke and colleagues on page 306. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Research Articles
Author Choice
Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer
Lillian M. Smyth; Sarina A. Piha-Paul; Helen H. Won; Alison M. Schram; Cristina Saura; Sherene Loi; Janice Lu; Geoffrey I. Shapiro; Dejan Juric; Ingrid A. Mayer; Carlos L. Arteaga; Macarena I. de la Fuente; Adam M. Brufksy; Iben Spanggaard; Morten Mau-Sørensen; Monica Arnedos; Victor Moreno; Valentina Boni; Joohyuk Sohn; Lee S. Schwartzberg; Xavier Gonzàlez-Farré; Andrés Cervantes; François-Clement Bidard; Alexander N. Gorelick; Richard B. Lanman; Rebecca J. Nagy; Gary A. Ulaner; Sarat Chandarlapaty; Komal Jhaveri; Elena I. Gavrila; Catherine Zimel; S. Duygu Selcuklu; Myra Melcer; Aliaksandra Samoila; Yanyan Cai; Maurizio Scaltriti; Grace Mann; Feng Xu; Lisa D. Eli; Melanie Dujka; Alshad S. Lalani; Richard Bryce; José Baselga; Barry S. Taylor; David B. Solit; Funda Meric-Bernstam; David M. Hyman
Resistance Mechanisms to SYK Inhibition in Acute Myeloid Leukemia
Anjali Cremer; Jana M. Ellegast; Gabriela Alexe; Elizabeth S. Frank; Linda Ross; S. Haihua Chu; Yana Pikman; Amanda Robichaud; Amy Goodale; Björn Häupl; Sebastian Mohr; Arati V. Rao; Alison R. Walker; James S. Blachly; Federica Piccioni; Scott A. Armstrong; John C. Byrd; Thomas Oellerich; Kimberly Stegmaier
Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15+ Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Claudia X. Dominguez; Sören Müller; Shilpa Keerthivasan; Hartmut Koeppen; Jeffrey Hung; Sarah Gierke; Beatrice Breart; Oded Foreman; Travis W. Bainbridge; Alessandra Castiglioni; Yasin Senbabaoglu; Zora Modrusan; Yuxin Liang; Melissa R. Junttila; Christiaan Klijn; Richard Bourgon; Shannon J. Turley
Author Choice
In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma
Fei Li; Qingyuan Huang; Troy A. Luster; Hai Hu; Hua Zhang; Wai-Lung Ng; Alireza Khodadadi-Jamayran; Wei Wang; Ting Chen; Jiehui Deng; Michela Ranieri; Zhaoyuan Fang; Val Pyon; Catríona M. Dowling; Ece Bagdatlioglu; Christina Almonte; Kristen Labbe; Heather Silver; Alexandra R. Rabin; Kandarp Jani; Aristotelis Tsirigos; Thales Papagiannakopoulos; Peter S. Hammerman; Vamsidhar Velcheti; Gordon J. Freeman; Jun Qi; George Miller; Kwok-Kin Wong
Gain-of-Function RHOA Mutations Promote Focal Adhesion Kinase Activation and Dependency in Diffuse Gastric Cancer
Haisheng Zhang; Antje Schaefer; Yichen Wang; Richard G. Hodge; Devon R. Blake; J. Nathaniel Diehl; Alex G. Papageorge; Matthew D. Stachler; Jennifer Liao; Jin Zhou; Zhong Wu; Fahire G. Akarca; Leonie K. de Klerk; Sarah Derks; Mariaelena Pierobon; Katherine A. Hoadley; Timothy C. Wang; George Church; Kwok-Kin Wong; Emanuel F. Petricoin; Adrienne D. Cox; Douglas R. Lowy; Channing J. Der; Adam J. Bass
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