City of Hope

Gerd P Pfeifer

Tibor A Rauch

John J Rossi

Xiwei Wu

Kevin V Morris

Daniela Castanotto

Zunde Wang

Reinhard Dammann

Stella Tommasi

Daniel H Kim

The present invention relates to transcriptional gene silencing (TGS) in mammalian, including human, cells that is mediated by small interfering RNA (siRNA) molecules. The present invention also relates to a double stranded nucleic acid that directs methylation of histones associated with target genes that produce low copy promoter-specific RNA. It has been found that siRNAs can be used to direct methylation of histones in mammalian, including human, cells.

Double stranded nucleic acid targeting low copy promoter-specific RNA

The present invention relates to the identification of novel DNA biomarkers and the use of the aberrant methylation patterns of the biomarkers to diagnose a disease or a condition (e.g., a cancer) associated therewith. In particular, the present invention relates to the use of the novel DNA biomarkers to diagnose lung cancers, e.g., squamous cell carcinomas and adenocarcinomas.

DNA methylation biomarkers for lung cancer

The present invention provides new and improved assay for detection of genomic methylated CpG islands. This new method is termed the methylated-CpG island recovery assay (MIRA). In accordance with one embodiment, MIRA comprises the steps of: (a) incubating genomic DNA fragments with a methylated CpG island binding protein in the presence of a binding partner for the binding protein to produce bound DNA containing methylated CpG islands, (b) isolating the bound DNA, and (c) detecting CpG island methylation by gene-specific amplification reactions. In accordance with a preferred embodiment, MIRA comprises the steps of: (a) incubating sonicated genomic DNA with a matrix containing a fusion protein of glutathione S-transferase (GST) and MBD2b (GST-MBD2b) in the presence of MBD3L1 to produce bound DNA containing methylated CpG islands, (b) eluting bound DNA from the matrix, and (c) detecting CpG island methylation by gene-specific amplification reactions.

Method for detecting methylated CpG islands

The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human tumor suppressor gene, termed RASSF1 herein. More specifically, the invention relates to the analysis of the RASSF1 gene and its use in the diagnosis of predisposition to cancer. The invention also relates to the prophylaxis and/or therapy of cancer associated with the RASSF1 gene. The invention further relates to the screening of drugs for cancer therapy. Finally, the invention relates to the screening of the RASSF1 gene for methylation, loss of heterozygosity or mutations, which are useful for diagnosing the predisposition to cancer.

Growing community of inventors

Duarte, CA, United States of America

Gerd P Pfeifer