TY - JOUR
T1 - Advances in functional genetic screening with transposons and CRISPR/Cas9 to illuminate cancer biology
AU - O'Donnell-Mendell, Kathryn A
N1 - Publisher Copyright:
© 2018 The Author
PY - 2018/4
Y1 - 2018/4
N2 - 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.
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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U2 - 10.1016/j.gde.2018.03.006
DO - 10.1016/j.gde.2018.03.006
M3 - Review article
C2 - 29587177
AN - SCOPUS:85044477318
SN - 0959-437X
VL - 49
SP - 85
EP - 94
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
ER -