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    Article

    Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers

    Although single-gene perturbation screens have revealed a number of new targets, vulnerabilities specific to frequently altered drivers have not been uncovered. An important question is whether the compensator...

    Takahiro Ito, Michael J. Young, Ruitong Li, Sidharth Jain in Nature Genetics (2021)

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    Article

    Bridging the gap between cancer cell line models and tumours using gene expression data

    Cancer cell line models are a cornerstone of cancer research, yet our understanding of how well they represent the molecular features of patient tumours remains limited. Our recent work provides a computationa...

    Javad Noorbakhsh, Francisca Vazquez, James M. McFarland in British Journal of Cancer (2021)

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    Article

    A first-generation pediatric cancer dependency map

    Exciting therapeutic targets are emerging from CRISPR-based screens of high mutational-burden adult cancers. A key question, however, is whether functional genomic approaches will yield new targets in pediatri...

    Neekesh V. Dharia, Guillaume Kugener, Lillian M. Guenther in Nature Genetics (2021)

  4. Article

    Author Correction: Cas9 activates the p53 pathway and selects for p53-inactivating mutations

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    Oana M. Enache, Veronica Rendo, Mai Abdusamad, Daniel Lam in Nature Genetics (2020)

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    Article

    Cas9 activates the p53 pathway and selects for p53-inactivating mutations

    Cas9 is commonly introduced into cell lines to enable CRISPR–Cas9-mediated genome editing. Here, we studied the genetic and transcriptional consequences of Cas9 expression itself. Gene expression profiling of ...

    Oana M. Enache, Veronica Rendo, Mai Abdusamad, Daniel Lam in Nature Genetics (2020)

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    Article

    The landscape of cancer cell line metabolism

    Despite considerable efforts to identify cancer metabolic alterations that might unveil druggable vulnerabilities, systematic characterizations of metabolism as it relates to functional genomic features and as...

    Haoxin Li, Shaoyang Ning, Mahmoud Ghandi, Gregory V. Kryukov in Nature Medicine (2019)

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    Article

    Small-molecule targeting of brachyury transcription factor addiction in chordoma

    Chordoma is a primary bone cancer with no approved therapy1. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutati...

    Tanaz Sharifnia, Mathias J. Wawer, Ting Chen, Qing-Yuan Huang in Nature Medicine (2019)

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    Article

    Mutational processes shape the landscape of TP53 mutations in human cancer

    Unlike most tumor suppressor genes, the most common genetic alterations in tumor protein p53 (TP53) are missense mutations1,2. Mutant p53 protein is often abundantly expressed in cancers and specific allelic vari...

    Andrew O. Giacomelli, ** Yang, Robert E. Lintner in Nature Genetics (2018)

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    Article

    Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry

    Childhood high-risk neuroblastomas with MYCN gene amplification are difficult to treat effectively1. This has focused attention on tumor-specific gene dependencies that underlie tumorigenesis and thus provide val...

    Adam D. Durbin, Mark W. Zimmerman, Neekesh V. Dharia, Brian J. Abraham in Nature Genetics (2018)

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    Article

    Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer

    Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency15. Here, we surveyed genome-scal...

    Srinivas R. Viswanathan, Marina F. Nogueira, Colin G. Buss in Nature Genetics (2018)

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    Article

    Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells

    CERES is a new computational method to estimate gene-dependency levels from CRISPR–Cas9 essentiality screens while accounting for copy number effects and variable sgRNA activity. Applying CERES to new genome-s...

    Robin M Meyers, Jordan G Bryan, James M McFarland, Barbara A Weir in Nature Genetics (2017)

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    Article

    SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2

    The authors identify EZH2 as a general underlying dependency of tumors with mutations in the SWI/SNF chromatin regulator complex, and they show that EZH2's pro-tumorigenic role may be dependent on non-catalyti...

    Kimberly H Kim, Woo** Kim, Thomas P Howard, Francisca Vazquez in Nature Medicine (2015)

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    Article

    The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis

    Matthew Freedman and colleagues show that androgen receptor (AR) binding sites undergo extensive reprogramming during prostate epithelial transformation. They further show that FOXA1 and HOXB13 colocalize at r...

    Mark M Pomerantz, Fugen Li, David Y Takeda, Romina Lenci, Apurva Chonkar in Nature Genetics (2015)

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    Article

    ARID1B is a specific vulnerability in ARID1A-mutant cancers

    Mutations inactivating ARID1A, a subunit of the chromatin remodeling SWI/SNF complex, have been identified in some human cancers. This study reveals that cancer cells with mutated ARID1A are dependent on the r...

    Katherine C Helming, **aofeng Wang, Boris G Wilson, Francisca Vazquez in Nature Medicine (2014)