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- 저자 : Minussi, Darlan Conterno (검색결과 1 건)
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Systematic Functional Annotation of Somatic Mutations in Cancer
Ng, Patrick Kwok-Shing,Li, Jun,Jeong, Kang Jin,Shao, Shan,Chen, Hu,Tsang, Yiu Huen,Sengupta, Sohini,Wang, Zixing,Bhavana, Venkata Hemanjani,Tran, Richard,Soewito, Stephanie,Minussi, Darlan Conterno,Mo Cell Press 2018 CANCER CELL Vol. No.
<P><B>Summary</B></P> <P>The functional impact of the vast majority of cancer somatic mutations remains unknown, representing a critical knowledge gap for implementing precision oncology. Here, we report the development of a moderate-throughput functional genomic platform consisting of efficient mutant generation, sensitive viability assays using two growth factor-dependent cell models, and functional proteomic profiling of signaling effects for select aberrations. We apply the platform to annotate >1,000 genomic aberrations, including gene amplifications, point mutations, indels, and gene fusions, potentially doubling the number of driver mutations characterized in clinically actionable genes. Further, the platform is sufficiently sensitive to identify weak drivers. Our data are accessible through a user-friendly, public data portal. Our study will facilitate biomarker discovery, prediction algorithm improvement, and drug development.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Developed a versatile functional genomic platform for somatic mutation annotation </LI> <LI> Annotated >1,000 genomic aberrations, doubling the number of known driver mutations </LI> <LI> Assessed performance of existing algorithms for mutation functional predictions </LI> <LI> Built a user-friendly, open-access data portal for community-based investigation </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
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