Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.

E-GEOD-64765 - Selective Loss of RB in Resistant EGFR Mutant Lung Adenocarcinomas that Transform to SCLC [CGH]

Status
Released on 30 January 2015, last updated on 8 February 2015
Organism
Homo sapiens
Samples (12)
Array (1)
Protocols (5)
Description
The study was designed to identify the molecular changes that occur in EGFR mutant NSCLCs that become resistant to TKI by transforming to SCLC. Tyrosine kinase inhibitors (TKIs) are effective treatments for non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However, they do not lead to cures, and, on average, relapse occurs after one year of continuous treatment. In a subset of patients, a fundamental histological transformation from NSCLC to small cell lung cancer (SCLC) is observed in the resistant cancers, but the molecular changes associated with this transformation remain unknown. Analysis of a cohort of tumor samples and cell lines derived from resistant EGFR mutant patients with SCLC transformation revealed that RB is lost in 100% of these cases, but rarely in those that remain NSCLC. Global changes in gene expression, including increased neuroendocrine marker expression and absence of EGFR expression, are observed in cancers that transformed to SCLC. Consistent with their genetic and epigenetic similarities to classical SCLC, cell lines derived from resistant EGFR mutant SCLC biopsies are substantially more sensitive to ABT-263 treatment compared to those derived from resistant EGFR mutant NSCLCs. Together, these findings suggest that despite developing initially as EGFR mutant adenocarcinomas, this subset of resistant cancers ultimately take on many of the molecular and phenotypic characteristics of classical SCLC. Overall, we completed array CGH analysis on 4 tumor specimens from EGFR mutant, TKI-resistant patients. Three of these samples had transformed to SCLC and one remained NSCLC.
Experiment type
comparative genomic hybridization by array 
Contacts
Kenneth N Ross <Ross.Kenneth@mgh.harvard.edu>, Anthony J Iafrate, Jeffrey A Engelman, Matthew J Niederst
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-64765.idf.txt
Sample and data relationshipE-GEOD-64765.sdrf.txt
Raw data (1)E-GEOD-64765.raw.1.zip
Processed data (1)E-GEOD-64765.processed.1.zip
Additional data (1)E-GEOD-64765.additional.1.zip
Array designA-GEOD-16237.adf.txt
Links