Cancer Genetics Flashcards
Cancer is a _____ process
Cancer is a genetic process!
- changes/variations occur in genes over time
- lifestyle, exposures, internal factors
The majority of caner is ______ 10% of cancer is ________ and 30% of cancer is _______-
the majority of cancer is sporadic, 10% of cancer is herditary and 30% of cancer is familial
WHat are the 2 kinds of herditary predispositions?
Germline: autosomal dominant
SOmatic: ‘two hit’
What are some red flags in a family history what the cancer may be hereditary
young age of dx
many affected family members
more than 1 generation
pairing of cancers in the family
more than one cancer in the same person
Ashkenazi Jewish heritage
what is the role of a cancer genetic counselor?
explore the psychological impact of genetic testing
work closely with insurance companies
address gentic discrimination concerns
introduce medical management options
talk about implications for family members
discuss the option of DNA banking
what are different testing methods
single site analsis
multisite analysis (Ashkenazi jew)
sequencing
deletion/duplication testing
Next Gen Sequencing: gene panels, whole exome, whole genome
What is Next Generation Sequencing?
- massive parallel sequencing
- create 100s to 1000s of reads per base pair
- provides enhanced resolution throughput and speed
- generates large amounts of data quickly in a cost effective manner
- sequence multiple genes simultaneously
- possible to detect mosaicism
Why would you use a NGS Multi-gene panel test?
- efficient sequencing of multiple genes
- many genes implicated in each cancer: testing multiple genes simultaneously can be more time and cost effective
- overlapping clinical presentation among different hereditary cancer syndromes
- many patients have negative BRCA1/2 genetic testing
what are the benefits to genetic testing?
provides risk info
provides infor useful for medical management
leads to early cancer prevention and detection
may relieve anxiety
what are the limitations of genetic testing
not able to detect all causes of hereditary cancer
continued risk for sporadic cancer
some management strategies not proven effective
What does a “positive” variant mean?
“inconclusive”
“negative”
positive: deleterious mutation, variant, likely pathogenic-interpret with caution
inconclsive: variant of undetermined significance
negative: variant, liely benign-interpret with caution. variant benign (polymorphism) not reported
What is the Genetic Information nondiscrimination Act (GINA)
- federal law passed in 2008 that protects individuals from genetic discrimination in health insuance and employment. does not apply to life insurance
How may germline mutations influence cancer treatment?
- Immunotherpay for colorectal cancer:
- checkpoint inhibitors (PD1)
- MSI-high tumors have many tumor infiltrating lymphocytes
- PARP inhibition in BRCA+ excision repair
- inhibition of base excision repair
- synthetic lethality in homologous recombination
who is the best person in a family to start genetic testing?
the most severly affected, youngest onset or more rare tumor type
initial gene testing may include____________ if multiple genes are implicated in a syndrome a ________ may be more cost effective
initial gene testing may include full gene sequencing and deletion/duplication analysis. if multiple genes are implicated in a syndrome, a next generation sequencing panel may be more cost effective as a front line test.
