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Driver fusions and their implications in the development and treatment of human cancers

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Title: Driver fusions and their implications in the development and treatment of human cancers
Authors: Gao, Q
Liang, W-W
Foltz, SM
Mutharasu, G
Jayasinghe, RG
Cao, S
Liao, W-W
Reynolds, SM
Wyczalkowski, MA
Yao, L
Yu, L
Sun, SQ
Chen, K
Lazar, AJ
Fields, RC
Wendl, MC
Van Tine, BA
Vij, R
Chen, F
Nykter, M
Shmulevich, I
Ding, L
Item Type: Journal Article
Abstract: Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy.
Issue Date: 3-Apr-2018
Date of Acceptance: 13-Mar-2018
URI: http://hdl.handle.net/10044/1/71268
DOI: https://doi.org/10.1016/j.celrep.2018.03.050
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 227
End Page: 238
Journal / Book Title: Cell Reports
Volume: 23
Issue: 1
Copyright Statement: © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
SQUAMOUS-CELL CARCINOMA
GENOMIC CHARACTERIZATION
MYELOID-LEUKEMIA
BREAST-CANCER
BCR-ABL
GENES
TUMORS
LANDSCAPES
MUTATIONS
PATHWAYS
RNA
cancer
fusion
gene fusions
translocation
Fusion Analysis Working Group
Cancer Genome Atlas Research Network
Science & Technology
Life Sciences & Biomedicine
Cell Biology
SQUAMOUS-CELL CARCINOMA
GENOMIC CHARACTERIZATION
MYELOID-LEUKEMIA
BREAST-CANCER
BCR-ABL
GENES
TUMORS
LANDSCAPES
MUTATIONS
PATHWAYS
Publication Status: Published
Online Publication Date: 2018-04-05
Appears in Collections:Department of Surgery and Cancer