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Genome Med. 2015 Dec 18;7:129. doi: 10.1186/s13073-015-0252-1.

Landscape of gene fusions in epithelial cancers: seq and ye shall find.

Author information

1
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. chakumar@umich.edu.
2
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. chakumar@umich.edu.
3
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. arul@umich.edu.
4
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. arul@umich.edu.
5
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. arul@umich.edu.
6
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. arul@umich.edu.
7
Department of Urology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. arul@umich.edu.
8
Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. arul@umich.edu.

Abstract

Enabled by high-throughput sequencing approaches, epithelial cancers across a range of tissue types are seen to harbor gene fusions as integral to their landscape of somatic aberrations. Although many gene fusions are found at high frequency in several rare solid cancers, apart from fusions involving the ETS family of transcription factors which have been seen in approximately 50% of prostate cancers, several other common solid cancers have been shown to harbor recurrent gene fusions at low frequencies. On the other hand, many gene fusions involving oncogenes, such as those encoding ALK, RAF or FGFR kinase families, have been detected across multiple different epithelial carcinomas. Tumor-specific gene fusions can serve as diagnostic biomarkers or help define molecular subtypes of tumors; for example, gene fusions involving oncogenes such as ERG, ETV1, TFE3, NUT, POU5F1, NFIB, PLAG1, and PAX8 are diagnostically useful. Tumors with fusions involving therapeutically targetable genes such as ALK, RET, BRAF, RAF1, FGFR1-4, and NOTCH1-3 have immediate implications for precision medicine across tissue types. Thus, ongoing cancer genomic and transcriptomic analyses for clinical sequencing need to delineate the landscape of gene fusions. Prioritization of potential oncogenic "drivers" from "passenger" fusions, and functional characterization of potentially actionable gene fusions across diverse tissue types, will help translate these findings into clinical applications. Here, we review recent advances in gene fusion discovery and the prospects for medicine.

PMID:
26684754
PMCID:
PMC4683719
DOI:
10.1186/s13073-015-0252-1
[Indexed for MEDLINE]
Free PMC Article

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