Promoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation

Aiderus, Aziz and Contreras-Sandoval, Ana M. and Meshey, Amanda L. and Newberg, Justin Y. and Ward, Jerrold M. and Swing, Deborah A. and Copeland, Neal G. and Jenkins, Nancy A. and Mann, Karen M. and Mann, Michael B. (2021) Promoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation. Cancers, 13 (2). p. 225. ISSN 2072-6694

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Abstract

A central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor gene mutations driving cellular transformation and tumor progression in the absence of oncogenic driver mutation(s). Multiple in vitro and in vivo gene inactivation screens have enhanced our understanding of the tumor suppressor gene landscape in various cancers. However, these studies are limited to single or combination gene effects, specific organs, or require sensitizing mutations. In this study, we developed and utilized a Sleeping Beauty transposon mutagenesis system that functions only as a gene trap to exclusively inactivate tumor suppressor genes. Using whole body transposon mobilization in wild type mice, we observed that cumulative gene inactivation can drive tumorigenesis of solid cancers. We provide a quantitative landscape of the tumor suppressor genes inactivated in these cancers and show that, despite the absence of oncogenic drivers, these genes converge on key biological pathways and processes associated with cancer hallmarks.

Item Type: Article
Subjects: Academic Digital Library > Medical Science
Depositing User: Unnamed user with email info@academicdigitallibrary.org
Date Deposited: 03 Jan 2023 08:08
Last Modified: 22 Feb 2024 03:58
URI: http://publications.article4sub.com/id/eprint/247

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