The genetic paradigm of cancer — that tumors arise as a consequence of the accumulation of mutations in genes controlling cell proliferation, differentiation or death — is now widely accepted. The purpose of this is lecture provide a review of current knowledge on the various types of cancer genes identified so far in different stages of tumor development. We will also address recent attempts t...

Proper placement of epigenetic marks on DNA and histones is fundamental to normal development, and perturbations contribute to a variety of disease states. Combinations of marks act together to control gene expression; therefore, detecting their colocalization is important, but because of technical challenges, such measurements are rarely reported. Instead, measurements of epigenetic marks are ...

The p53 tumor suppressor gene is highly mutated in human cancers. Individuals who inherit one p53 mutant allele are susceptible to a wide range of tumor types, including breast cancer and sarcoma. We recently generated p53 knockout rats through gene targeting in embryonic stem cells. Here we show that rats homozygous for the null allele are prone to early onset spontaneous sarcomas and lymphoma...

Ovarian cancer is one of the most deadly malignancies in women because of its poor prognosis and that a majority of patients are diagnosed at advanced stage. Therefore, chemotherapy becomes the most important treatment option in most ovarian cancer cases. However, chemoresistance in relapsed cases is the major obstacle for the clinical management of this disease. Mounting evidences have suggest...

Glioblastoma multiforme is one of the most aggressive human cancers, and the most common primary, adult CNS neoplasm. Effective treatment strategies are lacking for these tumors, which carry a dismal prognosis. Transgenic mouse models have emerged as powerful tools for studying the biology of glioma [1]. Mice have been engineered to study the effects of manipulating genes and signaling pathways...

Epigenetic changes, including H3K4me3 and H3K27me3 histone modification, play an important role in carcinogenesis. However, no genome-wide histone modification map has been generated for gliomas. Here, we report a genome-wide map of H3K4me3 and H3K27me3 histone modifications for 8 glioma stem cell (GSC) lines, together with the associated gene activation or repression patterns. In addition, we ...

Canonical Wnt signaling plays a rate-limiting role in regulating self-renewal and differentiation in mouse embryonic stem cells (ESCs). We have previously shown that mutation in the Apc (adenomatous polyposis coli) tumor suppressor gene constitutively activates Wnt signaling in ESCs and inhibits their capacity to differentiate towards ecto-, meso-, and endodermal lineages. However, the underlyi...

The principal cause of human liver cancer is infection with hepatitis viruses B and C, but tumor progression is fueled by ensuing perturbations that confer gain of function on proto-oncogenes or loss of function on tumor suppressor genes. Frequent among these perturbations is overexpression of the proto-oncogene MET. We have modeled the pathogenesis of liver tumors by expressing conditional tra...

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite improvements in surgical, radiation and chemotherapy treatments, the overall survival of UM and prognosis remain poor. In the present study, we hypothesized that Sirtuin 1 and 2 (SIRT1/2), class III histone deacetylases (HDACs), were critical in controlling the destiny of bulk tumor cells and cancer stem cells (CSC...