Journal article
Driver Fusions and Their Implications in the Development and Treatment of Human Cancers
Cell reports (Cambridge), Vol.23(1), pp.227-238.e3
04/03/2018
DOI: 10.1016/j.celrep.2018.03.050
PMCID: PMB5916809
PMID: 29617662
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.
Details
- Title: Subtitle
- Driver Fusions and Their Implications in the Development and Treatment of Human Cancers
- Creators
- Qingsong Gao - Washington University in St. LouisWen-Wei Liang - Washington University in St. LouisSteven M Foltz - Washington University in St. LouisGnanavel Mutharasu - Tampere University of TechnologyReyka G Jayasinghe - Washington University in St. LouisSong Cao - Washington University in St. LouisWen-Wei Liao - Washington University in St. LouisSheila M Reynolds - Institute for Systems BiologyMatthew A Wyczalkowski - Washington University in St. LouisLijun Yao - Washington University in St. LouisLihua Yu - H3 Biomedicine, Inc., Cambridge, MA 02139, USA.Sam Q Sun - Washington University in St. LouisKen Chen - The University of Texas MD Anderson Cancer CenterAlexander J Lazar - The University of Texas MD Anderson Cancer CenterRyan C Fields - Washington University in St. LouisMichael C Wendl - Washington University in St. LouisBrian A Van Tine - Washington University in St. LouisRavi Vij - Washington University in St. LouisFeng Chen - Washington University in St. LouisMatti Nykter - University of TampereIlya Shmulevich - Institute for Systems BiologyLi Ding - Washington University in St. Louis
- Contributors
- Fusion Analysis Working Group (Contributor)Cancer Genome Atlas Research Network (Institution)Deqin Ma (Contributor) - University of Iowa, PathologyMohammed M Milhem (Contributor) - University of Iowa, Internal MedicineAaron D Bossler (Contributor) - University of Iowa, Pathology
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.23(1), pp.227-238.e3
- DOI
- 10.1016/j.celrep.2018.03.050
- PMID
- 29617662
- PMCID
- PMB5916809
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- U24 CA143843 / NCI NIH HHS R01 CA180006 / NCI NIH HHS R01 CA178383 / NCI NIH HHS U24 CA210957 / NCI NIH HHS U54 HG003079 / NHGRI NIH HHS P30 CA016672 / NCI NIH HHS U24 CA143883 / NCI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA143799 / NCI NIH HHS R50 CA221675 / NCI NIH HHS U24 CA143867 / NCI NIH HHS U24 CA143858 / NCI NIH HHS U24 CA143882 / NCI NIH HHS U54 HG003067 / NHGRI NIH HHS U24 CA143845 / NCI NIH HHS U24 CA143835 / NCI NIH HHS U54 HG003273 / NHGRI NIH HHS U24 CA143840 / NCI NIH HHS U24 CA211006 / NCI NIH HHS U24 CA144025 / NCI NIH HHS U24 CA143866 / NCI NIH HHS U24 CA210950 / NCI NIH HHS U24 CA210949 / NCI NIH HHS U24 CA143848 / NCI NIH HHS R01 CA163722 / NCI NIH HHS
- Language
- English
- Date published
- 04/03/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984185174002771
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