RT Journal Article
SR Electronic
T1 High-throughput detection of alternative splicing in patients with non-small cell lung cancer treated by bevacizumab/erlotinib
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 402
VO 44
IS Suppl 58
A1 Florent Baty
A1 Martin Brutsche
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/402.abstract
AB IntroductionAlternative splicing is an important component of tumorigenesis. Recent advent of exon array technology enables the detection of alternative splicing at a genome-wide scale. Few analysis tools of high-throughput alternative splicing are currently available. We propose a novel statistical approach for the detection of splicing changes in exon array data. Using this methodology, we investigated the genome-wide alteration of alternative splicing in NSCLC patients treated by bevacizumab/erlotinib.MethodsWe used restricted constrained correspondence analysis (RCCA) to explore the exonic variations with respect to disease phenotypes. We applied RCCA on oncological data investigating the response to targeted therapy on late stage non-squamous NSCLC. Exonic expression levels were measured on bronchospic biopsies from 42 patients treated by bevacizumab/erlotinib using Affymetrix GeneChip Human Exon 1.0 ST Array. Patients were categorized into responders/non-responders according to their response to treatment.ResultsSplicing candidates reveal a series of genes related to carcinogenesis, cell adhesion, tumor aggressiveness, apoptosis, proliferation and differentiation, as well as tumor growth or tumor suppression, with indication of known alternative splicing in a majority of genes. Diagnostic markers of metastasis and micrometastasis were also found.ConclusionRCCA facilitates the identification of biologically relevant alternative splicing events in high-throughput exon array data. The flexibility of this approach makes it ideal as a screening procedure for identification of splicing sites candidates and group-specific alternative splicing events.