Cancer is a disease that results from genetic changes (changes to the patients' DNA). Understanding the genetic changes that take place in cancer allow us understand the disease. As technology improves, it is easier (and less expensive) to idenfity the exact changes that have occured in any particular cancer patient. The development of new, targeted drugs means that knowing the exact genetic changes in any given patient is increasingly important in determining the right treatments for that individual. The tests currently available are able to predict how likely a particular cancer is to respond to a chemotherapy drug or how likely the cancer is to come back (recur) after it has been removed.
Diagnostic tests are able to examine:
1. The presence/absence/amount of a specific protein.
Examples of this include blood tests (CEA, CA-125) and tests performed on tumor samples obtained by biopsies (ER, HER2/neu). These types of tests have been available for many years and are routinely performed on patient samples.
2. The activity (expression) of a gene or set of genes.
The 'expression' of a gene refers to its transcription from DNA to RNA. All genes are not expressed equally in every cell; some may not be expressed at all. Cells express only the genes they require at any given time to survive and perform necessary functions. Altered gene expression is part of the process by which normal cells become cancerous. Extensive research is being performed to identify ways to monitor gene expression more effectively. Knowledge of which genes are aberrantly expressed in cancerous tissues has great potential to benefit cancer patients and even to help in cancer prevention.
Testing for gene expression by older methods only allows monitoring of a few genes at a time. GeneChip® analysis allows researcher to monitor hundreds to thousands of genes simultaneously. By monitoring many genes at once, sets of genes can be recognized as having altered expression. GeneChip® analysis employs a small quartz chip to which known fragments of DNA are attached. The DNA fragments on the chip may represent all of the genes in a cell.
The technology utilizes RNA purified from cells. Using an enzymatic process, the RNA is copied into DNA (cDNA) and the cDNA is labeled with a fluorescent (colored)dye. A control sample of normal tissue is treated in a similar fashion, with a dye of a different color. Aliquots of both samples are added to the array on the chip, to allow complementary nucleotides in the nucleic acid strands to pair with each other. RNA from genes that are expressed at a high level in cancer cells will be present in the samples at higher levels. The cDNA from these genes will bind to the gene chip in larger numbers and will exhibit more fluorescence. Levels of fluorescence for the genes on the chip are compared to determine which genes are expressed at higher and lower levels in cancerous tissues. Using mathematical approaches, sets of genes that have changes in their expression organized into groups.
Collectively, the display is referred to as an expression pattern. It is hoped that these expression patterns can be used to:
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Create diagnostic tests that are less invasive or are better indicators in early stage disease.
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Help identify new targets for treatment.
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Provide a means to better classify cancers.
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Allow for the generation of personalized treatment plans.
Several different companies are involved in creating/exploiting this technology. Affymetrix was one of the first companies involved. Learn more about GeneChip® technology from Affymetrix.
3. Genetic abnormalities (mutations) and epigenetic changes:
Mutations are changes to the DNA that alter the sequence of bases (A, C, G, and T) in our genes. Changes to critical genes are known to occur in cancer and new tests are being designed to identify these changes in tumor samples. The exact combination of changes found may make it likely that a particular treatment will work or is unlikely to have an impact. Epigenetic changes are also modifications to the bases, but they don't change the actual sequence. It is more like switching a lowercase a to uppercase A. The result is still altered gene activity and these changes are frequently seen in cancer.
New research has shown that it is possible to sequence the entire genome of cancer patients to find all possible changes in a timely and cost effective manner. This opens the door to many new diagnostic tests.
Learn more about mutations. Learn more about epigenetic changes.
Several molecular tests are available both inside and outside of the hospital setting. These 'direct to consumer' or DTC tests do not always need approval by the Food and Drug Administration (FDA) and caution is always urged for any tests of this nature. As in any medical test, it is important to understand how to interpret the results. As an example - if the results indicate that a persons' risk for developing a particular cancer is increased by 100% ( a two-fold increase) - what does that mean? If only one in 10,000 people without the identified risk get the disease, then the result means that the new risk is still only 1 in 5000 people. It is important to understand 'relative risk' (2 fold increase) vs 'absolute risk' (1 in 5000).
Molecular diagnostic tests that are currently available include:
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Mammaprint® - A test to determine the likelihood that breast cancer will recur.
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Oncotype DX® (breast cancer) - A test to determine which chemotherapy drugs are likely to be effective and the likelihood that the cancer will recur within 10 years.
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Oncotype DX® (colon cancer) - A test to determine the likelihood the cancer will recur. Used only for stage 2 colon cancer.
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