Nucleic Acids Research Advance Access originally published online on October 16, 2008
Nucleic Acids Research 2008 36(20):6535-6547; doi:10.1093/nar/gkn697
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Nucleic Acids Research, 2008, Vol. 36, No. 20 6535-6547
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer
1Department of Pathology, 2Department of Cardiothoracic Surgery, Mount Sinai School of Medicine, New York, NY 10029 and 3Heart, Lung and Esophageal Surgery Institute, and Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA
*To whom correspondence should be addressed. Tel: 585 273 3112; Fax: 585 276 2576; Email: tony_godfrey{at}urmc.rochester.edu
Received August 25, 2008. Revised September 24, 2008. Accepted September 25, 2008.
Alternative processing of pre-mRNA transcripts is a major source of protein diversity in eukaryotes and has been implicated in several disease processes including cancer. In this study we have performed a genome wide analysis of alternative splicing events in lung adenocarcinoma. We found that 2369 of the 17 800 core Refseq genes appear to have alternative transcripts that are differentially expressed in lung adenocarcinoma versus normal. According to their known functions the largest subset of these genes (30.8%) is believed to be cancer related. Detailed analysis was performed for several genes using PCR, quantitative RT-PCR and DNA sequencing. We found overexpression of ERG variant 2 but not variant 1 in lung tumors and overexpression of CEACAM1 variant 1 but not variant 2 in lung tumors but not in breast or colon tumors. We also identified a novel, overexpressed variant of CDH3 and verified the existence and overexpression of a novel variant of P16 transcribed from the CDKN2A locus. These findings demonstrate how analysis of alternative pre-mRNA processing can shed additional light on differences between tumors and normal tissues as well as between different tumor types. Such studies may lead to the development of additional tools for tumor diagnosis, prognosis and therapy.
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