Biomarker Testing

Biomarker testing is at the center of personalized medicine. The word "biomarker" refers to any of your body's molecules that can be measured to assess your health. Molecules can be obtained from your blood, body fluids, or tissue. Biomarker testing is a group of tests that looks for these molecular signs of health so that doctors can plan the best care. Biomarker testing may also be called "molecular testing" or "genetic testing."

Cancer occurs because of abnormal changes within the human genome. The human genome is the plan—like a blueprint—by which our bodies are made and work. It is found in most cells of your body.

The genome is made up of chromosomes. Chromosomes are long strands of DNA (deoxyribonucleic acid) that are tightly wrapped around proteins. DNA is a molecule that is shaped like a twisted ladder. Each step of the ladder is made of either one of two pairs of chemicals. Within the ladder are genes. Genes are instructions to make a product, usually protein.

Cancer biomarkers include structural changes within the genome, abnormal features of gene products, or biochemical effects of the tumor. Cancer biomarkers are used for many different aspects of cancer care. Some cancer biomarkers are used to assess a person's chances for developing cancer. Other cancer biomarkers are used for early detection (screening) and identification (diagnosis) of cancer. After a cancer diagnosis, biomarkers can be used to plan the best treatment. For example, biomarker testing is sometimes used to know if targeted therapy would treat cancer. Biomarkers may also be used to track treatment results or cancer growth if not on treatment.

For some biomarker tests, you should first see a genetic counselor. Genetic counselors can give you information and guidance about testing so that you can make an informed decision about whether to get tested. If you will undergo biomarker testing, you may also want to check if your insurance covers the test.

Biomarker tests can be divided into three groups: chromosome, gene, and biochemical. Each of these groups is described below. In addition, examples of each type of test are given.

Chromosome tests

Humans normally have 23 pairs of chromosomes. Chromosome tests look for abnormal changes within chromosomes. Such changes include parts of a chromosome being erased, expanded, or switched. Abnormal changes in chromosomes often occur in cancer cells. Translocation is one of the abnormal changes sometimes found in cancer cells. Translocation is the attachment of a piece of one chromosome to another chromosome. The hallmark of chronic myelogenous leukemia is the Philadelphia chromosome, which is created by translocation.

The Philadelphia chromosome is made of parts from chromosome 9 and 22. The short bottom piece of chromosome 9 and the short top piece of chromosome 22 attach to one another. See Figure 1. This translocation creates a longer chromosome 9 and a shorter chromosome 22. The shorter chromosome 22 is called the Philadelphia chromosome. As a result of this translation, the ABL gene from chromosome 9 and the BCR gene from chromosome 22 join together and form the BCR-ABL fusion gene.

Bone marrow cytogenetics is one type of chromosome test. It is also called conventional cytogenetics. It is used to detect the Philadelphia chromosome and measure the number of cells that have it.

Philadelphia Chromosome

Figure 1. Philadelphia chromosome

Gene tests

Gene tests assess either one gene or a short piece of DNA. These tests look for extra gene copies (duplicated or amplified genes), missing genes (gene deletions), or incorrectly placed genes (translocated genes). Also, gene tests can assess for small changes, such as an altered chemical "step" within the DNA "ladder," called gene mutations.

In normal breast or esophageal cells, there are two copies of the gene that makes HER2 (human epidermal growth factor receptor 2). HER2 is a protein found within the membrane of cells. When HER2 is activated, it causes breast and esophageal cancer cells to grow and divide. Some breast and esophageal cancers have cells with more than two copies of the HER2 gene causing too many HER2 receptors to be made. The gene test for HER2 is ISH (in situ hybridization). ISH counts the number of copies of the HER2 gene. If the cancer cells have too much HER2, targeted therapy may be used to treat the cancer.

Some non-small lung cancers have overactive EGFRs (epidermal growth factor receptors). Like HER2, EGFR is a protein found within the membrane of cells. When activated, it causes lung cancer cells to grow and divide. There are multiple gene mutations that can cause EGFRs to be overactive. DNA mutational analysis is a test that looks for the gene mutations that cause overactive EGFRs. Targeted therapies for lung cancer with mutant EGFR are also available.

Biochemical tests

Due to mutations, sometimes the proteins made by genes are also abnormal. There can be too many proteins or the proteins may be overactive as described above. These abnormal proteins help to promote cancer growth. Instead of using gene tests, doctors may look for abnormal proteins with biochemical tests.

As discussed before, some people with breast or esophageal cancer have more than two copies of the gene that makes HER2, which leads to an increase in the number of HER2 proteins. With too many HER2 proteins, the cancer cells multiply fast. IHC (immunohistochemistry) is the test used to count the number of HER2 receptors. Cancer cells with more than two HER2 gene copies or too many HER2 receptors are called "HER2 positive."

Other biochemical tests look for possible effects of cancer. Such tests include blood chemistry tests, which assess the level of chemicals in the blood. For example, chronic myelogenous leukemia, melanoma, multiple myeloma, and prostate cancer can cause high levels of lactate dehydrogenase in the blood. Blood chemistry tests can show if lactate dehydrogenase levels drop during cancer treatment. If so, your doctors will know that cancer treatment is working.