Recent translational research: Oncogene discovery by insertional mutagenesis gets a new boost

John Hilkens

doi:10.1186/bcr1376

Abstract

Knowledge of the genes and genetic pathways involved in onco-genesis is essential if we are to identify novel targets for cancer therapy. Insertional mutagenesis in mouse models is among the most efficient tools to detect novel cancer genes. Retrovirus-mediated insertional mutagenesis received a tremendous boost by the availability of the mouse genome sequence and new PCR methods. Application of such advances were limited to lympho-magenesis but are now also being applied to mammary tumourigenesis. Novel transposons that allow insertional muta-genesis studies to be conducted in tumors of any mouse tissue may give cancer gene discovery a further boost.

Highlights

Oncogenic transformation of a normal cell is a multistep process that requires activation or inactivation, usually by mutagenic events, of several key genes controlling various essential cellular pathways that are involved in growth and development
Comparison of the loci tagged by mammary tumour virus (MMTV) in mammary tumours identified in our own recent semi-high-throughput study (Theodorou V, Boer M, Kimm M, Theelen W, Jonkers J, Hilkens J, unpublished data) with the loci tagged by Moloney murine leukaemia virus (MoMuLV) in murine lymphomas deposited in the mouse Retrovirus Tagged Cancer Gene Database [13] suggests that the overlap is small
Retroviral insertional mutagenesis (IM) has already proven to be invaluable for this purpose and transposon-mediated IM will broaden further its application to malignancies other than lymphomas and mammary tumours

Summary

Introduction

Oncogenic transformation of a normal cell is a multistep process that requires activation or inactivation, usually by mutagenic events, of several key genes controlling various essential cellular pathways that are involved in growth and development. Retroviral insertional mutagenesis (IM) in mouse models is among the most efficient tools to uncover cancer genes. Because proviral integration is essentially random with some bias for transcriptionally active domains, retroviral insertions in the same genomic locus in multiple independent tumours mark a so-called common insertion site (CIS), which is likely to contain a gene involved in tumourigenesis.

Results

Conclusion