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New tools for functional mammalian cancer genetics

Abstract

Knowledge of the function of individual genes that encode components of cell-signalling pathways is crucial to our understanding of normal growth control and its deregulation in cancer, but we have functional information for only 15% of human genes at present. Several new technologies have recently become available to identify gene function in mammalian cells using high-throughput genetic screens. These new tools will make it possible to identify new and innovative classes of anticancer drugs, including those that show synthetic lethal interactions with cancer-specific mutations.

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Figure 1: Retroviral cDNA library screen.
Figure 2: RNA interference.
Figure 3: Loss-of-function screens using RNAi.

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Acknowledgements

We thank R. Beijersbergen for helpful discussions and critical reading of this manuscript and apologize to our colleagues for omission of relevant work due to space constraints. The work of the authors was supported by grants from the Dutch Cancer Society, The Netherlands Organization for Scientific Research and the Center for Biomedical Genetics.

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Correspondence to René Bernards.

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DATABASES

LocusLink

ARF

β-catenin

BRCA1

CBP

CYLD

env

gag

Hedgehog

ID4

ING1

KRAS

MDM2

MYC

NF-κB

p300

p53

pol

PPAN

PTEN

RAF1

RB

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Brummelkamp, T., Bernards, R. New tools for functional mammalian cancer genetics. Nat Rev Cancer 3, 781–789 (2003). https://doi.org/10.1038/nrc1191

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