Genomics

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Genes expression in xenografts obtained from 15 months cigarette smoke condensate (CSC)-exposed HBEC cells following expression of KRASV12


ABSTRACT: We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) 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 manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE101862 | GEO | 2017/10/21

SECONDARY ACCESSION(S): PRJNA395727

REPOSITORIES: GEO

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