Advances in functional genetic screening with transposons and CRISPR/Cas9 to illuminate cancer biology

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5 Citations (Scopus)

Abstract

Large-scale genome sequencing studies have identified a wealth of mutations in human tumors and have dramatically advanced the field of cancer genetics. However, the functional consequences of an altered gene in tumor progression cannot always be inferred from mutation status alone. This underscores the critical need for complementary methods to assign functional significance to mutated genes in cancer. Transposons are mobile genetic elements that serve as powerful tools for insertional mutagenesis. Over the last decade, investigators have employed mouse models with on-demand transposon-mediated mutagenesis to perform unbiased genetic screens to identify clinically relevant genes that participate in the pathogenesis of human cancer. Two distinct DNA transposon mutagenesis systems, Sleeping Beauty (SB) and PiggyBac (PB), have been applied extensively in vivo and more recently, in ex vivo settings. These studies have informed our understanding of the genes and pathways that drive cancer initiation, progression, and metastasis. This review highlights the latest progress on cancer gene identification for specific cancer subtypes, as well as new technological advances and incorporation of the CRISPR/Cas9 toolbox into transposon-mediated functional genetic studies.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalCurrent Opinion in Genetics and Development
Volume49
DOIs
StatePublished - Apr 1 2018

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Clustered Regularly Interspaced Short Palindromic Repeats
Genetic Testing
Neoplasms
Neoplasm Genes
Mutagenesis
Interspersed Repetitive Sequences
Genes
Beauty
Mutation
DNA Transposable Elements
Insertional Mutagenesis
Research Personnel
Genome
Neoplasm Metastasis

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

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title = "Advances in functional genetic screening with transposons and CRISPR/Cas9 to illuminate cancer biology",
abstract = "Large-scale genome sequencing studies have identified a wealth of mutations in human tumors and have dramatically advanced the field of cancer genetics. However, the functional consequences of an altered gene in tumor progression cannot always be inferred from mutation status alone. This underscores the critical need for complementary methods to assign functional significance to mutated genes in cancer. Transposons are mobile genetic elements that serve as powerful tools for insertional mutagenesis. Over the last decade, investigators have employed mouse models with on-demand transposon-mediated mutagenesis to perform unbiased genetic screens to identify clinically relevant genes that participate in the pathogenesis of human cancer. Two distinct DNA transposon mutagenesis systems, Sleeping Beauty (SB) and PiggyBac (PB), have been applied extensively in vivo and more recently, in ex vivo settings. These studies have informed our understanding of the genes and pathways that drive cancer initiation, progression, and metastasis. This review highlights the latest progress on cancer gene identification for specific cancer subtypes, as well as new technological advances and incorporation of the CRISPR/Cas9 toolbox into transposon-mediated functional genetic studies.",
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AB - Large-scale genome sequencing studies have identified a wealth of mutations in human tumors and have dramatically advanced the field of cancer genetics. However, the functional consequences of an altered gene in tumor progression cannot always be inferred from mutation status alone. This underscores the critical need for complementary methods to assign functional significance to mutated genes in cancer. Transposons are mobile genetic elements that serve as powerful tools for insertional mutagenesis. Over the last decade, investigators have employed mouse models with on-demand transposon-mediated mutagenesis to perform unbiased genetic screens to identify clinically relevant genes that participate in the pathogenesis of human cancer. Two distinct DNA transposon mutagenesis systems, Sleeping Beauty (SB) and PiggyBac (PB), have been applied extensively in vivo and more recently, in ex vivo settings. These studies have informed our understanding of the genes and pathways that drive cancer initiation, progression, and metastasis. This review highlights the latest progress on cancer gene identification for specific cancer subtypes, as well as new technological advances and incorporation of the CRISPR/Cas9 toolbox into transposon-mediated functional genetic studies.

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