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000156972 1001_ $$aWeber, Julia$$b0
000156972 245__ $$aIn vivo functional screening for systems-level integrative cancer genomics.
000156972 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2020
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000156972 500__ $$a2020 Oct;20(10):573-593
000156972 520__ $$aWith the genetic portraits of all major human malignancies now available, we next face the challenge of characterizing the function of mutated genes, their downstream targets, interactions and molecular networks. Moreover, poorly understood at the functional level are also non-mutated but dysregulated genomes, epigenomes or transcriptomes. Breakthroughs in manipulative mouse genetics offer new opportunities to probe the interplay of molecules, cells and systemic signals underlying disease pathogenesis in higher organisms. Herein, we review functional screening strategies in mice using genetic perturbation and chemical mutagenesis. We outline the spectrum of genetic tools that exist, such as transposons, CRISPR and RNAi and describe discoveries emerging from their use. Genome-wide or targeted screens are being used to uncover genomic and regulatory landscapes in oncogenesis, metastasis or drug resistance. Versatile screening systems support experimentation in diverse genetic and spatio-temporal settings to integrate molecular, cellular or environmental context-dependencies. We also review the combination of in vivo screening and barcoding strategies to study genetic interactions and quantitative cancer dynamics during tumour evolution. These scalable functional genomics approaches are transforming our ability to interrogate complex biological systems.
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000156972 7001_ $$0P:(DE-He78)19484c34bd0a338b52b4c22786721676$$aBraun, Christian J$$b1$$udkfz
000156972 7001_ $$0P:(DE-He78)ff492c619ece40dbfbc80b938bb5deb0$$aSaur, Dieter$$b2$$udkfz
000156972 7001_ $$0P:(DE-He78)340f7c2dcaedeae68e4a62c281c7350b$$aRad, Roland$$b3$$udkfz
000156972 773__ $$0PERI:(DE-600)2060549-3$$a10.1038/s41568-020-0275-9$$n10$$p573-593$$tNature reviews / Cancer Cancer$$v20$$x1474-1768$$y2020
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