Understanding the Genomics and Genetics of Cancer

Treating cancer is no longer one size fits all. Doctors now know that cancer is as unique as the person that has it since cancer develops when genes start 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 blueprint for the growth and control of cells. And one answer to understanding and treating cancer is through genomic testing.

Also referred to as molecular testing or tumor profiling, genomic testing is performed in a laboratory on samples of tumor tissue or blood. This form of testing enables doctors to learn about the tumor's genome, which is a full set of its DNA. By unlocking the DNA code of the tumor, doctors can better understand its unique features. Genomic testing is not conducted for every individual or cancer type. In the cases where this testing has a clinical benefit, some of the possible uses include the following:

• Diagnosing and staging a cancer
• Identifying prognosis (overview)
• Assessing whether treatments are available to treat mutations in that specific cancer
• Choosing treatment
• Tracking treatment effectiveness
• Watching for progression or recurrence
• Predicting how the tumor might behave, such as how fast-growing it is and how likely it is to spread (metastasize).

This technique to treat cancer is more personalized and accurate than traditional treatment methods. Benefits of using genomic testing include delivering a more precise diagnosis, choosing more precise treatments and sparing people with slow-growing disease from aggressive treatments that can have many side effects.

This guide focuses mainly on explaining what genomic testing is in an easy-to-understand way, and it gives a quick explanation of genetic testing.

What are mutations?

The foundation of genomic testing is built on finding mutations (changes that occur in the DNA of a cell). It is important to understand that just like everyone has a specific mix of genes that are unique to them, cancers are driven by a mixture of specific mutations.

Mutations are generally described as one of two kinds. They can be acquired during an individual's lifetime from environmental factors, such as tobacco use, ultraviolet radiation, viruses and age; or they are hereditary (inherited from a parent).

Acquired mutations are the most common cause of cancer. These mutations may be caused by mistakes during cell division or by exposure to DNA-damaging agents in the environment. They can be harmful, beneficial or have no impact. Particular mutations may lead to cancer or other diseases. A mutation is sometimes called a variant.

Testing for acquired and inherited mutations through genomic and genetic testing is transforming how doctors look at and treat cancer. By using new advanced technologies, doctors can now locate mutations in the genes that are causing your particular cancer. This approach to treating cancer is also known as precision medicine or precision oncology.

What is Genomic Testing?

Genomic testing for cancer developed as a result of the Human Genome Project. This project was led by a global team of researchers attempting to sequence and map all of the genes-- together called the genome-- of human beings.

Sequencing is a technique that researchers use to determine the order of the four chemical building blocks-- called "bases"-- that comprise the DNA molecule. DNA refers to the molecules inside cells that carry genetic info that is passed from one generation to the next through offspring. Nearly every cell in the body has a complete copy of the genome, which includes all the information needed for a person to develop and grow.

Genomic testing is normally done during the diagnostic process to detect biomarkers, which are substances such as genes or molecules that can be measured in the blood, plasma, urine, cerebrospinal fluid or other body fluids or tissues. Biomarkers are produced by cancer cells or other cells of the body in response to cancer. They are routinely tested for in particular cancers.

Testing for biomarkers is referred to as molecular testing. This type of testing is not used for every cancer diagnosis. Your doctor will speak with you if it may be beneficial for your treatment strategy (see Table 1).

It can also be done during treatment or if the cancer returns. When a tumor returns, it may have different mutations than before, which might impact treatment options.

A variety of tests are used to find genomic mutations, and the tests your doctor chooses might depend on the kind of cancer you have and the known mutations associated with it. This testing is typically done on tumor tissue (biopsy) and sometimes blood (liquid biopsy). Liquid biopsies test a sample of blood to identify circulating cancer cells shed from the tumor or pieces of DNA from the tumor, and check those cells for mutations. Liquid biopsies are increasingly being used due to the ease and convenience of taking a blood sample versus a tissue sample. Tissue and liquid biopsy results are included in the pathology report.

Choosing Treatment

Understanding the types of mutations your tumor has will help you make educated decisions with your doctor regarding your treatment options. If a mutation is located, your doctor will select a treatment that may target your cancer's specific mutation. But not all mutations have uniquely approved treatments available. If the testing does not identify a biomarker for which a specialized treatment exists, standard of care and clinical trials will be the options to take into consideration. Ongoing trials are investigating treatments for more mutations, which might give individuals the opportunity to get leading-edge treatments.

When genomic testing is used to choose a certain treatment option, the results help doctors identify whether an individual may benefit from certain types of drug therapy.

Targeted therapy is a kind of systemic therapy that targets genes, proteins or other factors that support the tumor. Genomic testing is used to determine whether any of the known targets in a patient's cancer exist that may respond to this treatment.

Immunotherapy uses the power and complexity of the body's natural immune system to locate and attack cancer cells. The objective is to target cancer cells solely, leaving healthy cells alone. Special testing helps identify whether an individual is a candidate for certain types of immunotherapy.

Chemotherapy travels via the bloodstream and impacts cells throughout the body. Since healthy cells along with cancer cells are impacted, some genomic tests are used to determine whether an individual's cancer will respond well to chemotherapy.

Hormone therapy blocks the stimulating effect of hormones. Genomic testing is used in cancers where hormones may be driving the cancer to determine whether hormone therapy might be beneficial.

Understanding Genetic Testing

The words genetic and genomic are often used interchangeably, but they have different objectives and outcomes. Genomic testing is used to understand your cancer for diagnosis, staging and treatment purposes, while genetic testing helps determine whether you have inherited a mutation that raises your risk for getting particular types of cancer-- even if you have not been diagnosed with cancer.

Genomic testing is done on a tumor sample or a liquid biopsy, and genetic testing may be done with a saliva or blood sample.

Numerous types of cancer, including breast, ovarian, thyroid, prostate, pancreatic, kidney and stomach cancers, along with melanoma and sarcoma, are known to run in families. If you have a family history of a particular form of cancer, you may consider genetic testing to learn whether you carry the corresponding gene. However, it is important to realize that if you have inherited a mutated gene, it does not mean you will automatically develop cancer; it only means the risk is increased and you can explore ways to reduce it, like surgery, medication, regular screenings or lifestyle adjustments.

The following risk factors may indicate that you have inherited an abnormal gene:

• Family history of cancer
• Cancer at an early age
• Multiple cancers in one family member
• Rare cancers
• Ancestry, like Ashkenazi Jewish heritage

Though some genetic tests are available to purchase without your doctor's participation, they are not advised for a person that might have cancer. The sensitivity of these tests is unknown compared to those used by doctors and designated laboratories, and the tests may not screen for all the possible genes and mutations for a certain cancer. The laboratories doctors use are regulated by the Clinical Laboratory Improvements Amendments program to satisfy standards for precision and dependability.

Choosing to have genetic testing is a decision that impacts your entire family. Knowing and sharing the information can help them be screened and observed closely if they have a gene mutation associated with cancer. Preventing or finding a cancer early offers the best opportunity of a successful treatment outcome.

The results might be complicated and difficult to interpret. A genetic counselor can help you through the testing process so you know what the results mean for you, your family members and their future health. Family members might be provided genetic testing if a mutation is discovered.

Special training enables a genetic counselor to guide you and your family members before and after you have genetic testing. The genetic counselor will review your medical history and cancer screening history, your family's cancer history, the possibility of an inherited cancer risk, the advantages and limitations of genetic testing, as well as current laws relating to the privacy of genetic information. The counselor can also help determine whether your health insurance will pay for the price of the test.

When you know your results, you can choose to share them with your kids, siblings, nieces, nephews, etc. However, be prepared that they might not wish to know or do anything about the information. Knowing these results can raise a range of emotions, including acceptance, relief, hope, confusion, denial, anger and guilt. Each family member has to make the decision about what to do with the information.

Depending on the resources available at each cancer facility, it is important to understand that a cancer genetic counselor may not be available. If one is not available at your cancer facility, ask your nurse navigator to refer to one that might be close by.

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