Title: Chronic Cigarette Smoke-Induced Epigenomic Changes Precede Sensitization of Bronchial Epithelial Cells to Single-Step Transformation by KRAS Mutations.

Authors: Vaz, Michelle; Hwang, Stephen Y; Kagiampakis, Ioannis; Phallen, Jillian; Patil, Ashwini; O'Hagan, Heather M; Murphy, Lauren; Zahnow, Cynthia A; Gabrielson, Edward; Velculescu, Victor E; Easwaran, Hariharan P; Baylin, Stephen B

Published In Cancer Cell, (2017 Sep 11)

Abstract: We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adenosquamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation.

PubMed ID: 28898697

MeSH Terms: No MeSH terms associated with this publication