Diagnostic Germline Testing Flashcards
Describe germline genetic testing
Mutation present in egg or sperm, inherited from parent, present in every cell of the body, testing typically performed on blood sample, identified inherited mutations that increase risk of developing cancer
Describe somatic genetic testing
Mutation that occurs after conception, not inherited from parent, not present in every cell (only found in subset of cells/tissue), testing typically performed on tumor sample, identified non-inherited mutations driving tumorigenesis
Types of germline genetic testing
Single-site, single gene, multi-gene panel, whole exome sequencing, whole genome sequencing, RNA sequencing
Who is the best individual in a family with a family history of cancer to undergo genetic testing?
Individuals who have been diagnosed with relevant types of cancer, especially at young ages
individuals who meet criteria or are at high risk
What are possible results from germline genetic testing?
Positive, true negative, negative/uninformative, VUS
What are the cancer risks and management for a positive genetic result?
Increased risk of cancer compared to general population, risk is specific to types of cancer related to gene
Disease management/surveillance/screening based on published guidelines. Cascade testing of family members initiated
What are the cancer risks and management for a true negative genetic result?
Tested individual does not have familial pathogenic variant, risk of cancer reduced to population risk
Disease management/surveillance/screening based on published guidelines
What are the cancer risks and management for a negative/uninformative genetic result?
Pathogenic variants may be present but not identified on test, individual/family may not have germline predisposition, cancer risk may be increased compared to population
Disease management/surveillance/screening should follow published guidelines based on family history
What are the cancer risks and management for a VUS genetic result?
Variant identified but unable to be categorized as pathogenic or benign, cancer risk may be increased
Disease management/surveillance/screening should follow published guidelines based on family history
What are measures of clinical validity
accuracy, precision, false positive rate, false negative rate, positive predictive value, negative predictive value, sensitivity, specificity
Risks of germline testing in cancer
depression/anxiety, strain on familial relationships, distress and uncertainty with inconclusive results, survivor guilt in patients with true negative results, unexpected results, genetic discrimination
Benefits of germline testing in cancer
Explain personal/family history of cancer, clearer risk assessment, informed management/surveillance plan, informs risk and genetic testing options for family members, reduce feelings of uncertainty for some patients
Limitations of germline testing cancer
Test results provide cancer risk, but cannot predict if an individual will actually develop cancer
If an individual has a negative result, it does not mean that they will never develop cancer
