1. The Department of Genetics, Cell Biology and Development, The Arnold and Mabel Beckman Center for Transposon Research, The Cancer Center, The University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA
2. †Present addresses: The Johns Hopkins School of Medicine, East Baltimore Campus, Ross 1064 – IM, 600 North Wolfe Street, Baltimore, Maryland 21287, USA (S.R.); Mouse Cancer Genetics Program, National Cancer Institute, Room 234, Building 539, 1050 Boyles Street, Frederick, Maryland 21702, USA (A.J.D.)
3. *These authors contributed equally to this work

Correspondence to: David A. Largaespada¹ Correspondence and requests for materials should be addressed to D.A.L. (Email: larga002@umn.edu).

Abstract

Retroviruses, acting as somatic cell insertional mutagens, have been widely used to identify cancer genes in the haematopoietic system and mammary gland^{1, 2}. An insertional mutagen for use in other mouse somatic cells would facilitate the identification of genes involved in tumour formation in a wider variety of tissues. Here we report the ability of the Sleeping Beauty transposon to act as a somatic insertional mutagen to identify genes involved in solid tumour formation. A Sleeping Beauty transposon, engineered to elicit loss-of-function or gain-of-function mutations, transposed in all somatic tissues tested and accelerated tumour formation in mice predisposed to cancer. Cloning transposon insertion sites from these tumours revealed the presence of common integration sites, at known and candidate cancer genes, similar to those observed in retroviral mutagenesis screens. Sleeping Beauty is a new tool for unbiased, forward genetic screens for cancer genes in vivo.

1. The Department of Genetics, Cell Biology and Development, The Arnold and Mabel Beckman Center for Transposon Research, The Cancer Center, The University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA
2. †Present addresses: The Johns Hopkins School of Medicine, East Baltimore Campus, Ross 1064 – IM, 600 North Wolfe Street, Baltimore, Maryland 21287, USA (S.R.); Mouse Cancer Genetics Program, National Cancer Institute, Room 234, Building 539, 1050 Boyles Street, Frederick, Maryland 21702, USA (A.J.D.)
3. *These authors contributed equally to this work

Correspondence to: David A. Largaespada¹ Correspondence and requests for materials should be addressed to D.A.L. (Email: larga002@umn.edu).

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