Advances in genomic testing technologies are allowing scientists to better understand multiple myeloma and the gene mutations that drive it. This is possible through various types of testing that analyze the cancer at a deeper level. Because certain abnormal genes and chromosomes are known to play a role in multiple myeloma, some abnormalities are now routinely looked for during the diagnostic process using genomic testing. Doctors use this information to diagnose and stage as well as select treatment options.
Understanding Genomic Testing
Ideally performed along with other diagnostic tests before treatment begins, genomic testing, sometimes referred to as molecular testing, is done in a laboratory using samples of blood or tissue to identify a tumor’s genome (a complete set of its DNA) and genetic mutations, which are changes in the cell’s DNA. The results can indicate the cancer’s behavior in response to different drug treatments. By unlocking the DNA code of the tumor, doctors can better understand its unique characteristics.
Specialized equipment will be used to sequence the tumor’s DNA and find any abnormalities. DNA sequencing determines the order of the four building blocks – called “bases” – that make up the DNA molecule. If abnormalities are found, they will be compared to known mutations. Results are returned to your doctor in a pathology report.
Genomic testing can also be done during treatment or if the cancer returns. When a tumor returns, it may have different mutations than before, which may affect treatment options.
The Role of Mutations
Cancer forms when genes begin to change, or mutate, within the structure of normal cells. Therefore, cancer is ultimately a disease of our genes, which are pieces of DNA — the information plan for the growth and control of cells. Genomic testing is built on finding mutations that occur in the DNA of a cell.
Just as every person has a specific, unique blend of genes, cancers are driven by a mixture of specific mutations. In multiple myeloma, chromosome mutations may indicate whether the disease is aggressive or not. In general, some types of the chromosome mutation that can lead to cancer include the following:
- Deletion — Part of the chromosome is missing or deleted.
- Duplication — Part of the chromosome is duplicated, resulting in extra genetic material.
- Inversion — Part of the chromosome has broken off, turned upside down and reattached.
- Rearrangement — Part of the chromosome has broken off and reattached, creating a different order of its genes, which may create a new gene.
- Rings — Part of the chromosome has broken off and formed a circle or ring.
- Translocation — Part of the chromosome is transferred to another chromosome.
Knowing whether you have chromosome mutations associated with multiple myeloma will help you to understand the aggressiveness of the disease and make informed decisions with your doctor about your treatment options. Some chromosome mutations found in multiple myeloma that may indicate a higher-risk form include the following:
- Deletion of part or all of chromosome 17
- Deletion of part or all of chromosome 13
- Translocation of part of chromosome 4 with part of chromosome 14
- Translocation between parts of chromosomes 14 and 16
- Translocation between parts of chromosomes 14 and 20
- Duplication/amplification or deletion of part of chromosome 1
It is possible for a patient to have more than one chromosome mutation at the same time, which increases the chance of a higher risk multiple myeloma.
Types of Testing Used
A variety of tests are used to discover key pieces of information that could affect your treatment options. The tests your doctor chooses may depend on your diagnosis, the information your doctor is seeking and the known mutations associated with multiple myeloma.
Some of the tests that may be performed on blood or bone marrow for diagnosis, or determining whether the multiple myeloma is high risk, include the following:
- Biomarkers are substances that can be measured in the blood, plasma, urine, cerebrospinal fluid or other body fluids or tissues. Biomarkers that are commonly tested for in multiple myeloma include albumin, beta-2-microglobulin and lactate dehydrogenase.
- Cytogenetics evaluates cells for chromosome abnormalities by looking for genetic changes at the DNA level in a bone marrow sample. Abnormalities, such as chromosomes that are broken, rearranged or missing, may indicate the level of disease. Cytogenetic analysis may help your doctor determine the treatment plan most likely to be effective for you.
- Flow cytometry measures the number of cells, the percentage of live cells and certain characteristics of cells, such as size and shape in a sample of blood or bone marrow. The presence of tumor markers/biomarkers, such as antigens, on the surface of cells is also measured. This aids in diagnosis.
- Fluorescence in situ hybridization (FISH) detects abnormal cells that may be associated with a more advanced myeloma. During the test, fluorescent dye is used to highlight genes or areas of chromosomes under a microscope to look for abnormalities that might have clinical implications.
- Immunohistochemistry uses antibodies to check for certain antigens in a sample of tissue. It may be used to help with diagnosis and to determine the difference between certain types of cancer.
- Measurable/minimum residual disease (MRD) testing determines the number of cancer cells that are present in bone marrow. “MRD positive” means disease is still detected. “MRD negative” means no disease is detected.