NDLI: Identification of mRNA isoform switching in breast cancer

Content Provider	Springer Nature : BioMed Central
Author	Zhao, Wei Hoadley, Katherine A. Parker, Joel S. Perou, Charles M.
Abstract	Background Alternative splicing provides a major mechanism to generate protein diversity. Increasing evidence suggests a link of dysregulation of splicing associated with cancer. While previous genomic-based studies demonstrated the expression of a handful of tumor-specific isoforms, genome-wide alterations in the balance between isoforms and cancer subtypes is understudied. Result We systematically analyzed the isoform-level expression patterns and isoform switching events of 819 breast tumor and normal samples assayed by mRNA-seq from TCGA project. On average, 2.2 isoforms per gene were detected and 67.5 % of detected genes (i.e. expressed) showed 1–2 isoforms only. While the majority of isoforms for a given gene were positively correlated with each other and the overall gene level, 470 pairs of isoforms displayed an inverse correlation suggesting a switching event. Most of the isoform switching events were associated with molecular subtypes, including a Basal-like-associated switching in CTNND1. 88 genes showed switching independent of subtypes, among which the isoform pattern of PRICKLE1 was associated with a large genomic signature of biological significance. Conclusion Our results reveal that the majority of genes do not undergo complex mRNA splicing within breast cancers, and that there is a general concordance in isoform and gene expression levels in breast tumors. We identified hundreds of isoform switching events across breast tumors, most of which were associated with differences in tumor subtypes. As exemplified by the detailed analysis of CTNND1 and PRICKLE1, these isoform switching events potentially provide new insights into the post-transcriptional regulatory mechanisms of tumor subtypes and cancer biology.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-016-2521-9.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/s12864-016-2521-9
Journal	BMC Genomics
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2016-03-03
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Alternative Splice Switching Event Alternative Splice Event Alternative Splice Site Nuclear Export Sequence
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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