Epigenetic mechanisms regulating leukemia stem cells (LSCs) are an attractive target for therapy of blood cancers. Here, we report that conditional knockout of the DNA methyltransferase Dnmt1 blocked development of leukemia, and haploinsufficiency of Dnmt1 was sufficient to delay progression of leukemogenesis and impair LSC self-renewal without altering normal hematopoiesis. Haploinsufficiency ...

Sustained transgene expression is required for the success of cell transplant-based gene therapy. Most widely used are lentiviral-based vectors which integrate into the host genome and thereby maintain sustained transgene expression. This requires integration into the nuclear genome, and potential risks include activation of oncogenes and inactivation of tumor suppressor genes. Plasmids have be...

The Drosophila tumor suppressor genes scribble, discs large and lethal giant larvae appear to act in a common pathway. Mutations in any of these genes lead to loss of apical-basal cell polarity and overproliferation of epithelia, revealing a close connection between cytoarchitecture and growth control.

Emerging data suggests that synthetic lethal interactions between mutated oncogenes/tumor suppressor genes and molecules involved in DNA damage signaling and repair can be therapeutically exploited to preferentially kill tumor cells. In this review, we discuss the concept of synthetic lethality, and describe several recent examples in which this concept was successfully implemented to target tu...

An efficient electrochemical approach is developed for ultrasensitive profiling of the methylation status of the p53 tumor suppressor gene based on a label-free biosensor in combination with bisulfite conversion.

Oncogenes and tumor suppressor genes (hereafter referred to as "cancer genes") result in cancer when they experience substitutions that prevent or distort their normal function. We examined evolutionary pressures acting on cancer genes and other classes of disease-related genes and compared our results to analyses of genes without known association to disease. We compared synonymous and nonsyno...

Although genomic sequencing has provided a better understating of the genetic landmarks in triple-negative breast cancer (TNBC), functional validation of candidate cancer genes (CCG) remains unsolved. In this study, we used a transposon mutagenesis strategy based on a two-step Sleeping Beauty (SB) forward genetic screen to identify and validate new tumor suppressors (TS) in this disease. We gen...

dna methylation plays an important role in carcinogenesis through epigenetic silencing of tumor suppressor genes. aberrant methylation usually results from changes in the activity of dna methyltransferases (dnmts). some studies show that the overexpression of the dnmts may lead to aberrant methylation of tumor suppressor genes. also the overexpression of dnmts may be related to methylation stat...

gastric cancer (gc) is the second most common cancer in the world and a leading cause of cancer-related mortality. methylation of promoter cpg islands (cgis) belonging to tumor suppressor genes causes transcriptional silencing of their corresponding genes leading to carcinogenesis and other disorders. adenomatous polyposis coli (apc) a tumor suppressor gene is inactivated by methylation of prom...