Systematic functional annotation of somatic mutations in cancer Journal Article

   


Authors: Ng, P. K. S.; Li, J.; Jeong, K. J.; Shao, S.; Chen, H.; Tsang, Y. H.; Sengupta, S.; Wang, Z.; Bhavana, V. H.; Tran, R.; Soewito, S.; Minussi, D. C.; Moreno, D.; Kong, K.; Dogruluk, T.; Lu, H.; Gao, J.; Tokheim, C.; Zhou, D. C.; Johnson, A. M.; Zeng, J.; Ip, C. K. M.; Ju, Z.; Wester, M.; Yu, S.; Li, Y.; Vellano, C. P.; Schultz, N.; Karchin, R.; Ding, L.; Lu, Y.; Cheung, L. W. T.; Chen, K.; Shaw, K. R.; Meric-Bernstam, F.; Scott, K. L.; Yi, S.; Sahni, N.; Liang, H.; Mills, G. B.
Article Title: Systematic functional annotation of somatic mutations in cancer
Abstract: 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. Ng et al. develop a moderate-throughput functional genomic platform and use it to annotate >1,000 cancer variants of unknown significance. The approach is sufficiently sensitive to identify weak drivers, potentially doubling the number of driver mutations characterized in clinically actionable genes. © 2018 Elsevier Inc.
Keywords: signal transduction; somatic mutation; biological marker; allele; gene amplification; epidermal growth factor receptor; wild type; carcinogenesis; algorithm; gene fusion; point mutation; growth factor; drug sensitivity; b raf kinase; therapeutic target; functional genomics; functional proteomics; tcga; indel mutation; priority journal; article; malignant neoplasm; cellular assay; clinical marker; driver mutation
Journal Title: Cancer Cell
Volume: 33
Issue: 3
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2018-03-12
Start Page: 450
End Page: 462.e10
Language: English
DOI: 10.1016/j.ccell.2018.01.021
PROVIDER: scopus
PUBMED: 29533785
PMCID: PMC5926201
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042855288&doi=10.1016%2fj.ccell.2018.01.021&partnerID=40&md5=497c86946825306c0e509830ba2acb2f
Notes: Article -- Export Date: 2 April 2018 -- Source: Scopus
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  1. Jianjiong Gao
    132 Gao
  2. Nikolaus D Schultz
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