Markers for Renal Cancer Diagnosis and Prognosis
Topics in This Section
CpG islands are found in the promoters of around half of all human genes. In normal cells and active genes, this CG sequence is typically not methylated. An epigenetic alteration involving methylation of the CG sequence leads to the silencing of genes, and some cancer cells manipulate this system to inactivate tumor suppressor genes. This aberrant silencing can be negated by drugs, such as 5-aza-2 deoxycytidine (5 Aza-dC) and Trichostatin A (TSA), which inhibit methyltransferase and histone deacetylase, respectively. These inhibitors are being employed along with microarray technology to examine the re-expression of silenced genes.
Dr. Paul Cairns is investigating new tumor suppressor genes aberrantly methylated in renal and other cancers using a demethylating drug to reactivate epigentically silenced genes in renal cancer cell lines. Using this approach, the IGFBP1, IGFBP3, and COL1A1 genes were validated and found to be habitually methylated in primary renal carcinoma as well as several other tumor types.
Applications and Advantages:
Many tumors are difficult to treat if they are diagnosed at an advanced stage, so methods that allow for early detection, such as gene methylation signature analysis, are desperately needed. Gene methylation has demonstrated great promise for early detection of cancer in body fluids that can be obtained by non-invasive methods. In addition, gene methylation evaluation has the potential benefit of allowing for tumor type specificity (differential diagnosis) and assessment of cancer risk. Also, this technology can result in the understanding of the mechanisms involved in cancer, suppressor gene pathways, and the response to certain therapies, as well as likelihood for recurrence. The dataset produced by the global reactivation screen can be further mined to gain insight into the methylome of the renal cancer cell and improve current panels for methylation-based detection as well as new markers for prediction of response and outcome.
A provisional patent application covering renal cancer has been filed in the U.S.