The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants
Open accessAbstract
Tumor-specific genomic information has the potential to guide therapeutic strategies and revolutionize patient treatment. Currently, this approach is limited by an abundance of disease-associated mutants whose biological functions and impacts on therapeutic response are uncharacterized. To begin to address this limitation, we functionally characterized nearly all (99.84%) missense mutants of MAPK1/ERK2, an essential effector of oncogenic RAS and RAF. Using this approach, we discovered rare gain- and loss-of-function ERK2 mutants found in human tumors, revealing that, in the context of this assay, mutational frequency alone cannot identify all functionally impactful mutants. Gain-of-function ERK2 mutants induced variable responses to RAF-, MEK-, and ERK-directed therapies, providing a reference for future treatment decisions. Tumor-associated mutations spatially clustered in two ERK2 effector-recruitment domains yet produced mutants with opposite phenotypes. This approach articulates an allele-characterization framework that can be scaled to meet the goals of genome-guided oncology.
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Analysis of protein-coding genetic variation in 60,706 humans
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Self-citationThe cancer genome atlas pan-cancer analysis project
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Discovery and saturation analysis of cancer genes across 21 tumour types
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“As a result, tumorassociated mutations have been detected in nearly all human genes and the number of uncharacterized mutations continues to rise (Lawrence et al., 2014).”
InfluentialSelf-citationInternational network of cancer genome projects
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A melanocyte lineage program confers resistance to MAP kinase pathway inhibition
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Self-citationDocking Motif Interactions in MAP Kinases Revealed by Hydrogen Exchange Mass Spectrometry
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“303 × 10−5, Fishers exact test) in ERK2 effector recruitment domains (Figure 5A) (Lee et al., 2004; Zhang et al., 2003).”
InfluentialSolution Structure of ERK2 Binding Domain of MAPK Phosphatase MKP-3
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Cited by
Comprehensive Characterization of Cancer Driver Genes and Mutations
Bailey, M. H., Tokheim, C., Porta-Pardo, E., Sengupta, S., Bertrand, D., Weerasinghe, A., Colaprico, A., Wendl, M. C., Kim, J., Reardon, B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.060 · Cited by 2,256
Self-citationLanguage models enable zero-shot prediction of the effects of mutations on protein function
Meier, J., Rao, R., Verkuil, R., Liu, J., Sercu, T., & Rives, A. (2021) · doi:10.1101/2021.07.09.450648 · Cited by 635
Deep generative models of genetic variation capture the effects of mutations
Riesselman, A. J., Ingraham, J. B., & Marks, D. S. (2018) · Nature Methods · doi:10.1038/s41592-018-0138-4 · Cited by 601
Mutational processes shape the landscape of TP53 mutations in human cancer
Giacomelli, A. O., Yang, X., Lintner, R. E., McFarland, J. M., Duby, M., Kim, J., Howard, T. P., Takeda, D. Y., Ly, S. H., Kim, E., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0204-y · Cited by 556
Self-citationImplementing Genome-Driven Oncology
Hyman, D. M., Taylor, B. S., & Baselga, J. (2017) · Cell · doi:10.1016/j.cell.2016.12.015 · Cited by 503
Metadata
- Authors
- Brenan, L., Andreev, A., Cohen, O., Pantel, S., Kamburov, A., Cacchiarelli, D., Persky, N. S., Zhu, C., Bagul, M., Goetz, E. M., Burgin, A. B., Garraway, L. A., Getz, G., Mikkelsen, T. S., Piccioni, F., Root, D. E., & Johannessen, C. M.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 17
- Issue
- 4
- Pages
- 1171-1183
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2535595233
- Cited by
- 160
- References
- 10
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- gold
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- Brenan, L., Andreev, A., Cohen, O., Pantel, S., Kamburov, A., Cacchiarelli, D., Persky, N. S., Zhu, C., Bagul, M., Goetz, E. M., Burgin, A. B., Garraway, L. A., Getz, G., Mikkelsen, T. S., Piccioni, F., Root, D. E., & Johannessen, C. M. (2016). Phenotypic Characterization of a Comprehensive Set of MAPK1/ERK2 Missense Mutants. Cell Reports. https://doi.org/10.1016/j.celrep.2016.09.061
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