Learn More
Retroviruses, acting as somatic cell insertional mutagens, have been widely used to identify cancer genes in the haematopoietic system and mammary gland. 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(More)
Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected(More)
Transposons have provided important genetic tools for functional genomic screens in lower eukaryotes but have proven less useful in higher eukaryotes because of their low transposition frequency. Here we show that Sleeping Beauty (SB), a member of the Tc1/mariner class of transposons, can be mobilized in mouse somatic cells at frequencies high enough to(More)
Human colorectal cancers (CRCs) display a large number of genetic and epigenetic alterations, some of which are causally involved in tumorigenesis (drivers) and others that have little functional impact (passengers). To help distinguish between these two classes of alterations, we used a transposon-based genetic screen in mice to identify candidate genes(More)
The Sleeping Beauty (SB) transposon system has been used as a somatic mutagen to identify candidate cancer genes. In previous studies, efficient leukemia/lymphoma formation on an otherwise wild-type genetic background occurred in mice undergoing whole-body mobilization of transposons, but was accompanied by high levels of embryonic lethality. To explore the(More)
The recent development of the Sleeping Beauty (SB) system has led to the development of novel mouse models of cancer. Unlike spontaneous models, SB causes cancer through the action of mutagenic transposons that are mobilized in the genomes of somatic cells to induce mutations in cancer genes. While previous methods have successfully identified many(More)
UNLABELLED Hepatocellular carcinoma (HCC) is associated with poor survival for patients and few effective treatment options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC. Because of the liver's unique affinity for small nucleic acids,(More)
We previously utilized a Sleeping Beauty (SB) transposon mutagenesis screen to discover novel drivers of HCC. This approach identified recurrent mutations within the Dlk1-Dio3 imprinted domain, indicating that alteration of one or more elements within the domain provides a selective advantage to cells during the process of hepatocarcinogenesis. For the(More)
Viral hepatitis, obesity, and alcoholism all represent major risk factors for hepatocellular carcinoma (HCC). Although these conditions also lead to integrated stress response (ISR) or unfolded protein response (UPR) activation, the extent to which these stress pathways influence the pathogenesis of HCC has not been tested. Here we provide multiple lines of(More)
Cutaneous squamous cell carcinoma (SCC) is the second most common form of cancer in the human population, yet the underlying genetic mechanisms contributing to the disease are not well understood. We recently identified Zmiz1 as a candidate oncogene in nonmelanoma skin cancer through a transposon mutagenesis screen. Here we show that transposon-induced(More)