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Genetic Abnormalities In Multiple Myeloma

Genetic Abnormalities in Multiple Myeloma

Research has shown that genetic factors may be linked to multiple myeloma. These factors are abnormalities in the number or structure of chromosomes. In addition, recent advances in technology and the mapping of the human genome have enabled scientists to discover that abnormalities in the expression, or levels, of some specific genes are associated with the risk for early relapse of myeloma. Both types of genetic abnormalities may help doctors predict the outcome of treatment.

Chromosome Abnormalities

Chromosome abnormalities may affect the number of chromosomes. For example, about half of all myeloma cases are linked to the deletion of chromosome 13. Abnormalities may also involve changes in structure. The most common structural abnormality in multiple myeloma is translocation, or mismatching of chromosome parts. Up to 40% of myeloma cases have been linked to one of five specific chromosome translocations.

These chromosome abnormalities may be an explanation for the wide variation in response to treatment among individuals with myeloma. Investigators are beginning to discover that some genetic subtypes of myeloma respond poorly to treatment. This means that chromosome abnormalities may become more widely used as a prognostic indicator, or a factor that allows physicians to predict the outcome of treatment. The discovery of chromosome abnormalities also presents opportunities to develop new drugs and other types of treatment that target the abnormality.

The examination of cells to look for chromosome abnormalities is called cytogenetic analysis. One cytogenetic method is karyotyping. With this technique, a sample from a bone marrow specimen is put into a special dish and allowed to grow in the laboratory. Plasma cells are then taken from the sample and stained. The stained cells are photographed and the image is analyzed to look for abnormal numbers or structures of chromosomes, such as deletions and translocations.

A more powerful way of analyzing cells for chromosome abnormalities is fluorescence in situ hybridization, commonly referred to as FISH. This testing method involves the use of a short piece of a single strand of DNA that has a specific chromosome abnormality (one associated with multiple myeloma). This piece of DNA is called a probe, and it is labeled with fluorescent dye. If cells in a person’s bone marrow sample have the same chromosome abnormality, the probe will bind to it. The fluorescent dye provides a way for the lab specialist to see exactly where the probe is attached to the chromosome.

Cytogenetic analysis is not routinely performed for all individuals with newly diagnosed myeloma, but a number of institutions are willing to perform the tests. Ask your doctor to recommend an appropriate testing site near you and your family. Cytogenetic analysis may provide you and your physician with more information about your prognosis and the possibility of treating your disease in targeted ways.

Abnormalities in Gene Expression

The identification of genes that, when abnormally expressed, are associated with risk for relapse has led to the development of a sophisticated test that provides a gene expression profile of a person’s myeloma. The gene expression profile is like a genetic fingerprint of a cancer, with each cancer being unique, just as each fingerprint is unique. More and more studies are showing that the gene expression profile of a cancerous tumor can help personalize treatment, and this test is the first one to be developed for myeloma.

The test, Myeloma Prognostic Risk Signature™ (MyPRS™), measures the expression values (levels) of 70 risk-related genes. A computer program then calculates a risk score based on these values. This risk score is unique to each person. The score is a prediction of whether an individual is at high risk or low risk for early relapse. Knowing the risk of relapse can help doctors know which patients are most likely to have a good response to treatment without relapse and which patients may benefit from more aggressive treatment, to help lower the risk of relapse.

The MyPRS™ test is new and is not yet routinely done. However, most experts agree that because the test provides such important information about relapse, it should be done at the time of diagnosis. Ask your doctor about gene expression profiling. Learn more about this test.