C03982: Genomic Screen for Epigenetically Silenced Genes Associated with Colorectal Cancer & Novel Biomarkers for the Detection & Diagnosis of Human Colorectal Cancer
Value Proposition:
Comprehensive biomarker panel for sensitive detection and diagnosis of colon and gastric cancers
Technical Details:
BACKGROUND
Although cancers generally are considered to be due to genetic changes such as mutations of a gene, it has become clear that epigenetic mechanisms, which do not result in mutations of the DNA sequence, also can result in cancers. The most commonly observed epigenetic change involves silencing of gene expression due to methylation of the gene sequence. Changes to genes that are associated with cancer, including mutations that result in loss of expression of gene or expression of a defective gene product, and epigenetic mechanisms such as methylation-silencing of gene transcription, provide markers useful for determining whether a cell is susceptible to loss of normal growth control and, therefore, potentially a cancer cell. As cancer often is a silent disease that does not present clinical signs or symptoms until the disease is well advanced, the availability and use of markers that allow the identification of individuals susceptible to a cancer, or even that allow detection of a cancer at an early stage, can be of great benefit. Unfortunately, such markers are not available for most cancers. As such, many cancer patients do not seek medical assistance until the cancer is at a stage that requires radical therapy, or is untreatable. Thus, a need exists for markers that can be used to detect cancer cells.
TECHNOLOGY
Researchers at the Johns Hopkins University have developed novel epigenetic biomarkers for early detection and diagnosis of human colorectal and gastric cancers. Aberrant hypermethylation of gene promoters is a major mechanism associated with inactivation of tumor-suppressor genes in cancer. We previously showed this transcriptional silencing to be mediated by both methylation and histone deacetylase activity, with methylation being dominant. Here, we have used cDNA microarray analysis to screen for genes that are epigenetically silenced in human colorectal cancer. By screening over 10,000 genes, we show that our approach can identify a substantial number of genes with promoter hypermethylation in a given cancer; these are distinct from genes with unmethylated promoters, for which increased expression is produced by histone deacetylase inhibition alone. Many of the hypermethylated genes we identified have high potential for roles in tumorigenesis by virtue of their predicted function and chromosome position. We also identified a group of genes that are preferentially hypermethylated in colorectal cancer and gastric cancer. One of these genes, SFRP1, belongs to a gene family; we show that hypermethylation of four genes in this family occurs very frequently in colorectal cancer, providing for (i) a unique potential mechanism for loss of tumor-suppressor gene function and (ii) construction of a molecular marker panel that could detect virtually all colorectal cancer.
Looking for Partners:
Commercial applications include molecular biomarkers useful for early and sensitive detection and diagnosis of colon and gastric cancer.
Publications/Associated Cases:
Suzuki, H., Gabrielson, E., Chen, W., Anbazhagan, R., Van Engeland, M., Weijenberg, M. P., et al. (2002). A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nature Genetics, 31(2), 141-149.
US 7794929 - Genomic screen for epigenetically silenced genes associated with cancer
