RNA sequencing of cancer reveals novel splicing alterations
Open Access
- 22 April 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 3 (1), srep01689-12
- https://doi.org/10.1038/srep01689
Abstract
Breast cancer transcriptome acquires a myriad of regulation changes, and splicing is critical for the cell to “tailor-make” specific functional transcripts. We systematically revealed splicing signatures of the three most common types of breast tumors using RNA sequencing: TNBC, non-TNBC and HER2-positive breast cancer. We discovered subtype specific differentially spliced genes and splice isoforms not previously recognized in human transcriptome. Further, we showed that exon skip and intron retention are predominant splice events in breast cancer. In addition, we found that differential expression of primary transcripts and promoter switching are significantly deregulated in breast cancer compared to normal breast. We validated the presence of novel hybrid isoforms of critical molecules like CDK4, LARP1, ADD3, and PHLPP2. Our study provides the first comprehensive portrait of transcriptional and splicing signatures specific to breast cancer sub-types, as well as previously unknown transcripts that prompt the need for complete annotation of tissue and disease specific transcriptome.This publication has 54 references indexed in Scilit:
- The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroupsNature, 2012
- BRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 yearsBritish Journal of Cancer, 2012
- Changes in aromatase (CYP19) gene promoter usage in non-small cell lung cancerLung Cancer, 2011
- Computational methods for transcriptome annotation and quantification using RNA-seqNature Methods, 2011
- Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiationNature Biotechnology, 2010
- Exonic expression profiling of breast cancer and benign lesions: a retrospective analysisThe Lancet Oncology, 2009
- Alternative isoform regulation in human tissue transcriptomesNature, 2008
- Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell linesNature Genetics, 2008
- Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot projectNature, 2007
- Understanding alternative splicing: towards a cellular codeNature Reviews Molecular Cell Biology, 2005