TY - JOUR
T1 - Driver Fusions and Their Implications in the Development and Treatment of Human Cancers
AU - The Fusion Analysis Working Group
AU - The Cancer Genome Atlas Research Network
AU - Gao, Qingsong
AU - Liang, Wen Wei
AU - Foltz, Steven M.
AU - Mutharasu, Gnanavel
AU - Jayasinghe, Reyka G.
AU - Cao, Song
AU - Liao, Wen Wei
AU - Reynolds, Sheila M.
AU - Wyczalkowski, Matthew A.
AU - Yao, Lijun
AU - Yu, Lihua
AU - Sun, Sam Q.
AU - Caesar-Johnson, Samantha J.
AU - Demchok, John A.
AU - Felau, Ina
AU - Kasapi, Melpomeni
AU - Ferguson, Martin L.
AU - Hutter, Carolyn M.
AU - Sofia, Heidi J.
AU - Tarnuzzer, Roy
AU - Wang, Zhining
AU - Yang, Liming
AU - Zenklusen, Jean C.
AU - Zhang, Jiashan (Julia)
AU - Chudamani, Sudha
AU - Liu, Jia
AU - Lolla, Laxmi
AU - Naresh, Rashi
AU - Pihl, Todd
AU - Sun, Qiang
AU - Wan, Yunhu
AU - Wu, Ye
AU - Cho, Juok
AU - DeFreitas, Timothy
AU - Frazer, Scott
AU - Gehlenborg, Nils
AU - Getz, Gad
AU - Heiman, David I.
AU - Kim, Jaegil
AU - Lawrence, Michael S.
AU - Lin, Pei
AU - Meier, Sam
AU - Noble, Michael S.
AU - Saksena, Gordon
AU - Voet, Doug
AU - Zhang, Hailei
AU - Bernard, Brady
AU - Chambwe, Nyasha
AU - Giama, Nasra
AU - Kocher, Jean Pierre
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/4/3
Y1 - 2018/4/3
N2 - 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. Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability.
AB - 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. Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability.
KW - RNA
KW - cancer
KW - fusion
KW - gene fusions
KW - translocation
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U2 - 10.1016/j.celrep.2018.03.050
DO - 10.1016/j.celrep.2018.03.050
M3 - Article
C2 - 29617662
AN - SCOPUS:85044744284
SN - 2211-1247
VL - 23
SP - 227-238.e3
JO - Cell reports
JF - Cell reports
IS - 1
ER -