How a Genetic Mutation Can Cause Cancer

Rachel Zohn | Nov 16, 2017

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Out of an estimated 1.3 million people living with colon and rectal cancer in the United States, researchers estimate that 15 percent have tumors associated with something called microsatellite instability (MSI). This means that a person’s genes are more likely to mutate and possibly cause cancer. MSI affects the way DNA replicates, which can eventually result in development of tumors in the colon and rectum, as well as in other parts of the body. If you have MSI biomarkers, you may be more susceptible to cancer.

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What are microsatellite biomarkers?

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Microsatellite biomarkers are repetitive segments of DNA we carry in our chromosomes. In normal microsatellite cells, the DNA mismatch repair system recognizes and repairs mutations that happen during DNA cell replication. The system functions like a spell checker, correcting typos. A deficient system fails to correct these “typos.” This results in DNA damage.

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How MSI tumors develop

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When the mutation repair system fails, cells can become damaged and mutate, which allows uncontrolled cell growth and tumors. Microsatellite tumors can be divided into three types: MSI-high (MSI-H), MSI-low, or microsatellite stable. MSI-H tumors have a high amount of instability, meaning the DNA in these tumors has a high level of mutations. And what can these cell mutations lead to? You guessed it: cancer.

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Areas of the body that are effected by this genetic mutation

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Tumors that result from this process may have hundreds to thousands of mutations found throughout the body. For instance, MSI-H tumors are more commonly found in colon, endometrial, and gastrointestinal cancers but can also be found in the lungs, bladder, and urinary tract, skin, thyroid, pancreas, breast, uterine, ovarian, and cervical cancers.

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Determining if a tumor is MSI-H

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An MSI screening test looks for changes in the DNA sequence between normal tissue and tumor tissue to identify whether there is a high amount of instability. About 15 percent of colorectal cancers are positive for MSI-H tumors. The mutations that cause these errors often happen sporadically but sometimes these tumors are associated with a hereditary condition known as Lynch syndrome.

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Tests to determine hereditary condition

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If it’s suspected that you have Lynch syndrome, your doctor may gather a family history of colon and other cancers in your family. An immunohistochemistry test (IHC) can determine if a tumor is caused by the hereditary Lynch syndrome, also known as nonpolyposis colorectal cancer. If positive, there is also a risk that your family members may have the condition as well.

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Cancer treatment options

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In general, MSI-H cancers are considered less aggressive than other types of tumors, and MSI-H patients have a more favorable prognosis. However, the mutations present in MSI-H tumors may make them resistant to some types of chemotherapy. Several studies have shown that MSI-H patients respond best to surgery alone, rather than chemotherapy and surgery. Also, many patients respond positively to immunotherapy treatments because MSI-H tumors attract the attention of the immune system.

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The immune system and cancer

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The immune system uses T cells to detect and fight against disease – including cancer. The immune system uses certain pathways to control T cells. However, some MSI-H cancer cells are able to “hide” from T-cell attacks by taking control of the pathways the immune system uses to defend itself.

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Enabling the immune system to fight against MSI-H tumors

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If you were to look under a microscope at an MSI-H tumor, you would see a large number of immune cells that are trying to attack the tumor, but are being blocked from fully doing their job. Treatment aims to target a cellular pathway that is found within immune cells and some cancer cells so the immune system can fight those cells.

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Individualized treatment plan

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Knowing the MSI status of a patient’s cancer, including whether MSI-H biomarkers are present, is essential in setting up an individualized treatment plan and helping doctors decide on the best course of action.