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Nucleic Acids Res. 2015 May 26;43(10):5130-44. doi: 10.1093/nar/gkv210. Epub 2015 Apr 23.

Identification of recurrent regulated alternative splicing events across human solid tumors.

Author information

1
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
2
Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Ein Karem, 91120 Jerusalem, Israel.
3
Raymond and Beverly Sackler School of Physics and Astronomy and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
4
Department of Pathology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
5
Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Ein Karem, 91120 Jerusalem, Israel erez.levanon@biu.ac.il.
6
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel erez.levanon@biu.ac.il.

Abstract

Cancer is a complex disease that involves aberrant gene expression regulation. Discriminating the modified expression patterns driving tumor biology from the many that have no or little contribution is important for understanding cancer molecular basis. Recurrent deregulation patterns observed in multiple cancer types are enriched for such driver events. Here, we studied splicing alterations in hundreds of matched tumor and normal RNA-seq samples of eight solid cancer types. We found hundreds of cassette exons for which splicing was altered in multiple cancer types and identified a set of highly frequent altered splicing events. Specific splicing regulators, including RBFOX2, MBNL1/2 and QKI, appear to account for many splicing alteration events in multiple cancer types. Together, our results provide a first global analysis of regulated splicing alterations in cancer and identify common events with a potential causative role in solid tumor development.

PMID:
25908786
PMCID:
PMC4446417
DOI:
10.1093/nar/gkv210
[Indexed for MEDLINE]
Free PMC Article

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