Sleeping Beauty Transposon Screen

Overview

The Sleeping Beauty (SB) transposon system is an insertional mutagenesis approach used in mice to identify cancer driver genes in vivo. The SB11 transposase mobilizes T2/Onc transposon cassettes (which contain a splice donor, splice acceptor, and poly-A sequences) throughout the genome, activating or inactivating genes at insertion sites. Tumors that arise are sequenced to identify common insertion sites (gCIS — Gaussian kernel convolution insertion sites), which nominate candidate oncogenes and tumor suppressors. When combined with experimental therapies (e.g., radiation), the system enables identification of therapy-resistance driver genes by comparing gCIS distributions between untreated and treated/recurrent tumors.

Used by

• Sleeping Beauty transposon-driven mouse model (Ptch+/−/Math1-SB11/T2Onc(2)) of Shh medulloblastoma subjected to subtotal resection plus 18 × 2 Gy craniospinal irradiation; gCIS analysis showed <5% overlap of clonal driver events between primary and recurrent tumors, paralleling the genetic divergence observed in matched patient samples PMID:26760213.

Notes

• gCIS analysis requires transposon-insertion sequencing and bioinformatic identification of statistically recurrent insertion sites.
• The model is restricted to the tumor lineage driven by the initiating oncogenic context (e.g., Ptch+/− for Shh medulloblastoma); conclusions may not generalize to other subgroups.
• Combination with surgical and radiotherapy interventions allows modeling of therapy-resistance evolution.

Sources

This page was processed by entity-page-writer on 2026-05-14.