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Your search keyword '"Scott, Kenneth L"' showing total 9 results
Start Over Author "Scott, Kenneth L" Journal cancer research
9 results on '"Scott, Kenneth L"'

1. POT1 Regulates Proliferation and Confers Sexual Dimorphism in Glioma

Author

Jalali, Ali, primary, Yu, Kwanha, additional, Beechar, Vivek, additional, Bosquez Huerta, Navish A., additional, Grichuk, Anthony, additional, Mehra, Deepika, additional, Lozzi, Brittney, additional, Kong, Kathleen, additional, Scott, Kenneth L., additional, Rao, Ganesh, additional, Bainbridge, Matthew N., additional, Bondy, Melissa L., additional, and Deneen, Benjamin, additional

Published
2021
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2. Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer

Author

Lu, Hengyu, primary, Villafane, Nicole, additional, Dogruluk, Turgut, additional, Grzeskowiak, Caitlin L., additional, Kong, Kathleen, additional, Tsang, Yiu Huen, additional, Zagorodna, Oksana, additional, Pantazi, Angeliki, additional, Yang, Lixing, additional, Neill, Nicholas J., additional, Kim, Young Won, additional, Creighton, Chad J., additional, Verhaak, Roel G., additional, Mills, Gordon B., additional, Park, Peter J., additional, Kucherlapati, Raju, additional, and Scott, Kenneth L., additional

Published
2017
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4. Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations

Author

Dogruluk, Turgut, primary, Tsang, Yiu Huen, additional, Espitia, Maribel, additional, Chen, Fengju, additional, Chen, Tenghui, additional, Chong, Zechen, additional, Appadurai, Vivek, additional, Dogruluk, Armel, additional, Eterovic, Agna Karina, additional, Bonnen, Penelope E., additional, Creighton, Chad J., additional, Chen, Ken, additional, Mills, Gordon B., additional, and Scott, Kenneth L., additional

Published
2015
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9. Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer.

Author

Hengyu Lu, Villafane, Nicole, Dogruluk, Turgut, Grzeskowiak, Caitlin L., Kong, Kathleen, Yiu Huen Tsang, Zagorodna, Oksana, Pantazi, Angeliki, Lixing Yang, Neill, Nicholas J., Young Won Kim, Creighton, Chad J., Verhaak, Roel G., Mills, Gordon B., Park, Peter J., Kucherlapati, Raju, and Scott, Kenneth L.

Subjects
*CANCER genetics, *ONCOGENES, *GENETIC engineering, *GENETIC mutation, *INDIVIDUALIZED medicine
Abstract

Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in The Cancer Genome Atlas datasets. In addition to confirming oncogenic activity of the known fusion oncogenes engineered by our construction strategy, we validated five novel fusion genes involving MET, NTRK2, and BRAF kinases that exhibited potent transforming activity and conferred sensitivity to FDA-approved kinase inhibitors. Our fusion construction strategy also enabled domain-function studies of BRAF fusion genes. Our results confirmed other reports that the transforming activity of BRAF fusions results from truncation-mediated loss of inhibitory domains within the N-terminus of the BRAF protein. BRAF mutations residing within this inhibitory region may provide a means for BRAF activation in cancer, therefore we leveraged the modular design of our fusion gene construction methodology to screen N-terminal domain mutations discovered in tumors that are wild-type at the BRAF mutation hotspot, V600. We identified an oncogenic mutation, F247L, whose expression robustly activated the MAPK pathway and sensitized cells to BRAF and MEK inhibitors. When applied broadly, these tools will facilitate rapid fusion gene construction for subsequent functional characterization and translation into personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Published
2017
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