STAG2-deficient Human Cell Lines to Screen Anticancer Compounds
Reference #: 2011-025
“Stromal Antigen 2 (STAG2) Compositions and Methods” describes a new tumor suppressor gene, which for the very first time links the STAG2 gene on the X chromosome and identifies a potential causal mechanism (STAG2 deficiency) for chromosomal instability , i.e., aneuploidy in cancer. The STAG2 gene influences the production of a protein structure called the ‘cohesin complex’, which plays a key role in correctly separating sister chromatids during cell division. Mutations in STAG2 mean that cells are more likely to have uneven numbers of chromosomes after division, leading to an increased risk that they will develop into cancer cells. This technology offers a STAG2-deficient human cell line that can be used as part of a diagnostic tool to identify one at risk of getting cancer, as well as a screening tool to detect anticancer compounds. These proprietary cell lines (H4 STAG2 KI, 42MGBA STAG2 KI, and HCT116 STAG2 KO) are paired with isogenic controls harboring either endogenous mutant STAG2 genes (H4, 42MGBA) or endogenous wild-type STAG2 genes (HCT116). These genetically engineered cells can be used in cell-based screens to identify drug candidates that specifically kill cells with mutated STAG2. This is known as an “isogenic” cell-based screen, as the only known change in the cell lines is the loss of STAG2. Accordingly, libraries may be screened for those compounds that differentially affect the isogenic cell lines.
- Paired STAG2-proficient and deficient cell lines to be used to screen libraries of compounds and/or small molecules that preferentially kill STAG2-deficient cancer cells, including the following cancers: gliobastoma multiforme, bone, Ewing’s sarcoma, melanoma, cervical, hematologic, kidney and others.
- Detects STAG2 mutations in cancers that might be used as a diagnostic for early cancer detection
- Identifies the 1st broad-spectrum cancer gene on the X chromosome.
- Identifies a causal link to cancer instability and aneuploidy.
Stage of Development
Development of cell based screen completed and ready for licensing.
D.A. Solomon, et al., “Mutational inactivation of STAG2 causes aneuploidy in human cancer,” Science, 333: 1039-43, 2011 www.sciencemag.org/content/333/6045/1039.full.pdf
Smith, Michael, et. al., “Gene Mutation Adds Chromosomes in Cancer Cell Lines,” MedPage Today, 2011 www.medpagetoday.com/Genetics/GeneralGenetics/28115
Gallagher, James, “Three Cancers Share Genetic Link,” BBC, 18 August 2011 http://www.bbc.co.uk/news/health-14562054
Akst, Jef, “Chromosomes and Cancer,” The Scientist, 18 August 2011 http://the-scientist.com/2011/08/18/chromosomes-and-cancer/
Brice, Philippa, “Mutations in key gene linked to different forms of cancer”, PHG Foundation, 23 August 2011, http://www.phgfoundation.org/news/9613/
Provisional Application filed by Georgetown University August 2011.