Risk Management & Treatment

DNA damage repair and cancer treatment

Certain genes are important for repairing DNA damage. These genes are sometimes referred to as "DNA damage repair" (DDR) genes. 

  • In a normal cell, a mutation in a DDR gene increase the chance that it will become cancer. This is why an inherited mutation in a gene that repairs DNA damage increases the risk for cancer.
  • In a cancer cell, a mutation in a DDR gene can keep it from repairing damage caused by treatment. This means that cancer cells with mutations in these genes may be more sensitive to certain treatments.

Two main types of DNA damage repair genes are linked to increased cancer risk and improved response to certain types of treatment: 

Genetic tests can identify people with an inherited mutation in a DDR gene. Biomarker tests can find tumor cells that have difficulty repairing these types of DNA damage. 


HRR and HRD-positive

Homologous Recombination Response (HRR) genes repair a type of DNA damage known as "double-stranded DNA breaks." Cancers with difficulty repairing this type of DNA damage are known as homologous recombination deficient (HRD) or sometimes "HRD-positive." Mutations in the following genes may lead to HRD tumors:

  • FANCL
  • RAD51B
  • CDK12
  • RAD54

 


Biomarker tests can identify HRD tumors by: 

  • testing tumor tissue for mutations in the genes listed above. 
  • testing tumor tissue for genomic instability that indicates an HRD tumor

Testing tumors for HRD can be important, because tumors that cannot repair double-stranded DNA damage may be sensitive to a type of targeted therapy known as PARP inhibitors


MSI-H and MMR-D 

"Mismatch repair" (MMR) genes repair DNA damage that occurs during cell division. Tumors with mutations in mismatch repair genes are called "MMR-Deficient" (MMR-D). MMR-D tumors have a cellular abnormality known as Microsatellite Instability or MSI-High. Mutations in the following genes are associated with MMR-D tumors: 

  • MLH1
  • MSH2
  • MSH6
  • PMS2
  • EPCAM 

Testing tumors for MMR-D or MSI-High can be important, because these tumors are more likely to respond to a type of immunotherapy known as immune checkpoint inhibitors


Biomarker tests for tumor mutations and genetic tests for inherited mutations

Some tumor biomarker tests look for gene mutations in cancer cells. These tests differ from genetic tests for inherited cancer risk.

As cells become cancerous, they develop many gene mutations that cause abnormal growth. These gene changes, which occur after you are born and throughout your life—are known as acquired or "somatic" mutations. Acquired mutations are different than inherited mutations, which are passed on from parent to child and are present at birth in every cell. 

Tumor biomarker tests can look for mutations in cancer cells. Genetic tests for inherited mutations look at normal cells in blood or saliva to find gene changes that are present from birth, passed from parents to children and are linked to increased risk for hereditary cancer.

Information provided by tumor testing and genetic testing may overlap. When someone with an inherited mutation develops cancer, their cancer cells will likely carry the same mutation. For example, a person born with a BRCA1 mutation will have that mutation in all of their cells. If they develop cancer, their cancer cells will likely also have the same BRCA1 mutation. If a person born with an inherited MSH6 mutation develops colorectal cancer, their cancer cells will have the same mutation and will likely also be MSI-High.  

Not all tumor biomarker tests can distinguish inherited mutations from acquired mutations. If your biomarker test shows a mutation, ask your doctor if it may be hereditary and if you should have genetic testing for an inherited mutation
 

Illustration of concept of the overlap between tumor <abbr
                data-toggle='tooltip'
                class='glossary-tip tt-biomarker'
                title='<p>A chemical in the body that can be measured. Doctors sometimes run tests to measure biomarker levels to diagnose or track a condition. CA125 is an example of a biomarker that can be elevated in women with ovarian cancer.&nbsp;</p>
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            >biomarker</abbr> testing and genetic testing

Last updated July 01, 2020