Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling. / Creixell, Pau; Schoof, Erwin M; Simpson, Craig D; Longden, James; Miller, Chad J; Lou, Hua Jane; Perryman, Lara; Cox, Thomas R; Zivanovic, Nevena; Palmeri, Antonio; Wesolowska-Andersen, Agata; Helmer-Citterich, Manuela; Ferkinghoff-Borg, Jesper; Itamochi, Hiroaki; Bodenmiller, Bernd; Erler, Janine T; Turk, Benjamin E; Linding, Rune.

In: Cell, 16.09.2015.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Creixell, P, Schoof, EM, Simpson, CD, Longden, J, Miller, CJ, Lou, HJ, Perryman, L, Cox, TR, Zivanovic, N, Palmeri, A, Wesolowska-Andersen, A, Helmer-Citterich, M, Ferkinghoff-Borg, J, Itamochi, H, Bodenmiller, B, Erler, JT, Turk, BE & Linding, R 2015, 'Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling', Cell. https://doi.org/10.1016/j.cell.2015.08.056

APA

Creixell, P., Schoof, E. M., Simpson, C. D., Longden, J., Miller, C. J., Lou, H. J., Perryman, L., Cox, T. R., Zivanovic, N., Palmeri, A., Wesolowska-Andersen, A., Helmer-Citterich, M., Ferkinghoff-Borg, J., Itamochi, H., Bodenmiller, B., Erler, J. T., Turk, B. E., & Linding, R. (2015). Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling. Cell. https://doi.org/10.1016/j.cell.2015.08.056

Vancouver

Creixell P, Schoof EM, Simpson CD, Longden J, Miller CJ, Lou HJ et al. Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling. Cell. 2015 Sep 16. https://doi.org/10.1016/j.cell.2015.08.056

Author

Creixell, Pau ; Schoof, Erwin M ; Simpson, Craig D ; Longden, James ; Miller, Chad J ; Lou, Hua Jane ; Perryman, Lara ; Cox, Thomas R ; Zivanovic, Nevena ; Palmeri, Antonio ; Wesolowska-Andersen, Agata ; Helmer-Citterich, Manuela ; Ferkinghoff-Borg, Jesper ; Itamochi, Hiroaki ; Bodenmiller, Bernd ; Erler, Janine T ; Turk, Benjamin E ; Linding, Rune. / Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling. In: Cell. 2015.

Bibtex

@article{221d35dd888a4ffeb2b9046bc0aa8737,

title = "Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling",

abstract = "Cancer cells acquire pathological phenotypes through accumulation of mutations that perturb signaling networks. However, global analysis of these events is currently limited. Here, we identify six types of network-attacking mutations (NAMs), including changes in kinase and SH2 modulation, network rewiring, and the genesis and extinction of phosphorylation sites. We developed a computational platform (ReKINect) to identify NAMs and systematically interpreted the exomes and quantitative (phospho-)proteomes of five ovarian cancer cell lines and the global cancer genome repository. We identified and experimentally validated several NAMs, including PKCγ M501I and PKD1 D665N, which encode specificity switches analogous to the appearance of kinases de novo within the kinome. We discover mutant molecular logic gates, a drift toward phospho-threonine signaling, weakening of phosphorylation motifs, and kinase-inactivating hotspots in cancer. Our method pinpoints functional NAMs, scales with the complexity of cancer genomes and cell signaling, and may enhance our capability to therapeutically target tumor-specific networks.",

author = "Pau Creixell and Schoof, {Erwin M} and Simpson, {Craig D} and James Longden and Miller, {Chad J} and Lou, {Hua Jane} and Lara Perryman and Cox, {Thomas R} and Nevena Zivanovic and Antonio Palmeri and Agata Wesolowska-Andersen and Manuela Helmer-Citterich and Jesper Ferkinghoff-Borg and Hiroaki Itamochi and Bernd Bodenmiller and Erler, {Janine T} and Turk, {Benjamin E} and Rune Linding",

year = "2015",

month = sep,

day = "16",

doi = "10.1016/j.cell.2015.08.056",

language = "English",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

}

RIS

TY - JOUR

T1 - Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling

AU - Creixell, Pau

AU - Schoof, Erwin M

AU - Simpson, Craig D

AU - Longden, James

AU - Miller, Chad J

AU - Lou, Hua Jane

AU - Perryman, Lara

AU - Cox, Thomas R

AU - Zivanovic, Nevena

AU - Palmeri, Antonio

AU - Wesolowska-Andersen, Agata

AU - Helmer-Citterich, Manuela

AU - Ferkinghoff-Borg, Jesper

AU - Itamochi, Hiroaki

AU - Bodenmiller, Bernd

AU - Erler, Janine T

AU - Turk, Benjamin E

AU - Linding, Rune

PY - 2015/9/16

Y1 - 2015/9/16

N2 - Cancer cells acquire pathological phenotypes through accumulation of mutations that perturb signaling networks. However, global analysis of these events is currently limited. Here, we identify six types of network-attacking mutations (NAMs), including changes in kinase and SH2 modulation, network rewiring, and the genesis and extinction of phosphorylation sites. We developed a computational platform (ReKINect) to identify NAMs and systematically interpreted the exomes and quantitative (phospho-)proteomes of five ovarian cancer cell lines and the global cancer genome repository. We identified and experimentally validated several NAMs, including PKCγ M501I and PKD1 D665N, which encode specificity switches analogous to the appearance of kinases de novo within the kinome. We discover mutant molecular logic gates, a drift toward phospho-threonine signaling, weakening of phosphorylation motifs, and kinase-inactivating hotspots in cancer. Our method pinpoints functional NAMs, scales with the complexity of cancer genomes and cell signaling, and may enhance our capability to therapeutically target tumor-specific networks.

AB - Cancer cells acquire pathological phenotypes through accumulation of mutations that perturb signaling networks. However, global analysis of these events is currently limited. Here, we identify six types of network-attacking mutations (NAMs), including changes in kinase and SH2 modulation, network rewiring, and the genesis and extinction of phosphorylation sites. We developed a computational platform (ReKINect) to identify NAMs and systematically interpreted the exomes and quantitative (phospho-)proteomes of five ovarian cancer cell lines and the global cancer genome repository. We identified and experimentally validated several NAMs, including PKCγ M501I and PKD1 D665N, which encode specificity switches analogous to the appearance of kinases de novo within the kinome. We discover mutant molecular logic gates, a drift toward phospho-threonine signaling, weakening of phosphorylation motifs, and kinase-inactivating hotspots in cancer. Our method pinpoints functional NAMs, scales with the complexity of cancer genomes and cell signaling, and may enhance our capability to therapeutically target tumor-specific networks.

U2 - 10.1016/j.cell.2015.08.056

DO - 10.1016/j.cell.2015.08.056

M3 - Journal article

C2 - 26388441

JO - Cell

JF - Cell

SN - 0092-8674

ER -

ID: 144492952

Niels Bohr Institute