Transcriptomics

Dataset Information

5

Copy number profiling of 92 human lung tumors on Affymetrix 100K SNP arrays


ABSTRACT: Copy number profiling of 92 human lung tumors on Affymetrix 100K SNP arrays was conducted in order to assess the interaction of common genomic alterations with response to targeted anti-cancer therapeutics. Class 1 phosphatidylinositol 3' kinase (PI3K) plays a major role in cell proliferation and survival in a wide variety of human cancers. Here we investigate biomarker strategies for PI3K pathway inhibitors in non-small-cell lung cancer (NSCLC). Molecular profiling of NSCLC tumor samples showed that copy number gains in PIK3CA and total loss of PTEN protein were common in squamous cell carcinoma samples, whereas LKB1 loss and mutations in KRAS and EGFR were common in adenocarcinomas. A panel of NSCLC cell lines characterized for alterations in the PI3K pathway was screened with PI3K and dual PI3K/mTOR inhibitors to assess the preclinical predictive value of candidate biomarkers. Cell lines harboring pathway alterations (RTK activation, PI3K mutation or amplification, PTEN loss) were exquisitely sensitive to the PI3K inhibitor GDC-0941. A dual PI3K/mTOR inhibitor had broader activity across the cell line panel and in tumor xenografts. The combination of GDC-0941 with paclitaxel, erlotinib, or a MEK inhibitor had greater effects on cell viability than PI3K inhibition alone. CONCLUSIONS: Candidate biomarkers for PI3K inhibitors have predictive value in preclinical models and show histology-specific alterations in primary tumors, suggesting that distinct biomarker strategies may be required in squamous compared with non-squamous NSCLC patient populations. Lung tumors were profiled on Affymetrix GeneChip Mapping 100K Set Arrays Tumor samples were profiled for copy number without any treatment of the tumor.

ORGANISM(S): Homo sapiens  

SUBMITTER: Mark Lackner  Carol O'Brien   Peter M Haverty   Jane Fridlyand   Peter Haverty   Jill Spoerke    

PROVIDER: E-GEOD-39793 | ArrayExpress | 2013-01-22

SECONDARY ACCESSION(S): GSE39793PRJNA171717

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models.

Spoerke Jill M JM   O'Brien Carol C   Huw Ling L   Koeppen Hartmut H   Fridlyand Jane J   Brachmann Rainer K RK   Haverty Peter M PM   Pandita Ajay A   Mohan Sankar S   Sampath Deepak D   Friedman Lori S LS   Ross Leanne L   Hampton Garret M GM   Amler Lukas C LC   Shames David S DS   Lackner Mark R MR  

Clinical cancer research : an official journal of the American Association for Cancer Research 20121107 24


Class 1 phosphatidylinositol 3-kinase (PI3K) plays a major role in cell proliferation and survival in a wide variety of human cancers. Here, we investigated biomarker strategies for PI3K pathway inhibitors in non-small-cell lung cancer (NSCLC).Molecular profiling for candidate PI3K predictive biomarkers was conducted on a collection of NSCLC tumor samples. Assays included comparative genomic hybridization, reverse-transcription polymerase chain reaction gene expression, mutation detection for PI  ...[more]

Similar Datasets

2010-12-16 | E-GEOD-26075 | ArrayExpress
2011-06-10 | E-GEOD-18252 | ArrayExpress
2012-03-27 | E-GEOD-14579 | ArrayExpress
2012-01-30 | E-GEOD-34957 | ArrayExpress
2013-10-22 | E-GEOD-41592 | ArrayExpress
2014-06-28 | E-GEOD-48260 | ArrayExpress
2014-05-01 | E-GEOD-20393 | ArrayExpress
2014-05-02 | E-TABM-359 | ArrayExpress
2014-05-01 | E-GEOD-20574 | ArrayExpress
2013-07-15 | E-GEOD-39281 | ArrayExpress