Driver Fusions and Their Implications in the Development and Treatment of Human Cancers
Gao, Q.; Liang, Wen Wei; Foltz, Steven M.; Mutharasu, Gnanavel; Jayasinghe, Reyka G.; Cao, S.; Liao, Wen Wei; Reynolds, Sheila M.; Wyczalkowski, Matthew A.; Yao, Lijun; Yu, L.; Sun, Sam Q.; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Z.; Yang, L.; Zenklusen, Jean C.; Zhang, H.; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Wan, Y.; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, J.; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, M.S.; Saksena, Gordon; Voet, Doug; Zhang, J.J.; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Nykter, Matti; Knijnenburg, Theo (2018)
Gao, Q.
Liang, Wen Wei
Foltz, Steven M.
Mutharasu, Gnanavel
Jayasinghe, Reyka G.
Cao, S.
Liao, Wen Wei
Reynolds, Sheila M.
Wyczalkowski, Matthew A.
Yao, Lijun
Yu, L.
Sun, Sam Q.
Caesar-Johnson, Samantha J.
Demchok, John A.
Felau, Ina
Kasapi, Melpomeni
Ferguson, Martin L.
Hutter, Carolyn M.
Sofia, Heidi J.
Tarnuzzer, Roy
Wang, Z.
Yang, L.
Zenklusen, Jean C.
Zhang, H.
Chudamani, Sudha
Liu, Jia
Lolla, Laxmi
Naresh, Rashi
Pihl, Todd
Wan, Y.
Wu, Ye
Cho, Juok
DeFreitas, Timothy
Frazer, Scott
Gehlenborg, Nils
Getz, Gad
Heiman, David I.
Kim, J.
Lawrence, Michael S.
Lin, Pei
Meier, Sam
Noble, M.S.
Saksena, Gordon
Voet, Doug
Zhang, J.J.
Bernard, Brady
Chambwe, Nyasha
Dhankani, Varsha
Nykter, Matti
Knijnenburg, Theo
2018
Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:fi:tty-201804271582Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:fi:uta-201806202064
https://urn.fi/urn:nbn:fi:tty-201804271582Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:fi:uta-201806202064
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [16929]