Genetics: 2-Hit Model Flashcards
What is the sporadic tumor model?
assumes that the patient starts out with 2 normal copies of the the tumor suppressor gene (TSG) and all malignant changes will occur as somatic mutations
What are the first and second “hits” to genes?
each hit is an independent mutational event that renders one allele nonfunctional
In sporadic tumors, what is the risk to family members?
nothing - because each mutation/hit was somatic
What is the major difference in hereditary vs. sporadic tumors?
in sporadic tumors, the TSG hits are somatic only and not passed on; in hereditary tumors/cancers, the individual inherits a first hit and thus every cell in the body is heterozygous for a nonfunctional TSG allele
In a person with hereditary cancer, where does the second hit to TSG occur?
Within the tumor cells only, hence the development of cancerous proliferation
The majority of hereditary cancers segregate through families as ____ ____. with ____ penetrance.
autosomal dominant; reduced
How would an individual with an inherited nonfunctional TSG allele not develop cancer?
by inheriting one hit (nonfunctional allele) and [somehow] avoiding the second hit needed to develop a tumor
True or false: cancer families are not at risk for sporadic tumors; any tumor they develop wouldn’t be sporadic since they are already heterozygous for the nonfunctional TSG alleles.
False - cancer families are STILL at risk for sporadic tumors since these are somatic mutations that occur (randomly)
What is the mutation rate like in many cancers?
High
Acquired [cancerous] somatic mutations will be passed on to where?
to its own daughter cells via clonal expansion only
What is a constitutional mutation?
mutation (cancerous) that occurs in all cells of the body, including germline and somatic; can be inherited r new mutations
In the case of hereditary cancers, a constitutional mutation confers a ____ risk of cancer.
high - because it’s in all cells and includes inherited mutation AND multiple acquired mutations.
What is a driver mutation?
mutations in “cancer genes” that confers growth advantage through effects on a critical pathway
Typically, there are ____ driver mutations per tumor.
multiple
What is a passenger mutation?
mutation in cancer cells that confers no apparent growth advantage; these random mutations are carried along by clonal expansion; “along for the ride”
