Non-invasive cancer diagnostics
Rubicon believes that detection of methylated cancer DNA in serum and urine are the best approaches for developing practical non-invasive tests for cancer. Methylated DNA (meDNA) is a very stable carrier of epigenetic information that is directly involved in tumor formation and progression. Genes that are often methylated in tumors are termed “tumor markers,” because their methylation can be used to detect the disease. Utilization of methylated DNA markers is superior to reliance on other types of markers for numerous reasons, including:
- methylation is directly responsible for regulation of many cancer genes;
- DNA is chemically and biologically more stable than RNA and many other types of markers;
- the levels of gene methylation in cancer cells is very constant and not subject to fluctuations as seen for expressed products such as RNA, proteins, and metabolites;
- meDNA assays are inherently very sensitive (MethylPlex can detect as little as 1 cancer cell in a mixture with 10,000 normal cells);
- The same meDNA markers are not only found in humoral sources such as serum and urine, but also from tissue-specific sources, such as biopsies, sputum, semen, and breast/lung/uterus lavage (for organ-specific testing); and
- meDNA is a universal analyte for diagnostics, because the same technology, instrumentation, and data analysis methods can be used to detect many types of cancer and other diseases.
Because there are many paths for cancer progression, different genes become methylated in different types of cancer, different individuals, and different stages of the disease. Therefore the methylation of any single gene is not sufficient information to prevent unacceptable levels of false negative or false positive test results. However, a test based on the pattern of methylation in a number of genes would have the high sensitivity and specificity needed for an accurate diagnosis and prognosis that would direct the physician to prescribe the earliest and most effective treatment. Academic studies of meDNA have shown that the patterns of methylation in about 50 genes in surgical biopsy tissues can be used as highly sensitive and specific tests for prostate, breast, colon, lung, and other cancer. These “epigenetic patterns” are indicative of the organ, type of tumor, stage, aggressiveness, and whether it is localized or has spread. The challenge is to implement a test for those genes using a non-invasive protocol. Currently, there are two significant barriers to non-invasive testing.
- First, current meDNA tests require a large amount of cancer DNA, which is often not present in the blood or urine of cancer patients, especially during the initial stages of disease or upon recurrence.
- Second, current meDNA tests use a special chemistry, called “bisulfite conversion,” and proprietary amplification technologies that make testing complicated and expensive.
The Rubicon MethylPlex technology has solved both of these problems by completely avoiding “bisulfite” chemistry and improving technical sensitivity by a factor of 10 — 100 times, so that the methylation of many genes can be reliably detected from serum and urine.
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