Lecture 23 - Cancer Genetics 1 (Hereditary Cancers) Flashcards
Many cancer-causing mutations target the _________, the period in G1 where cells commit to enter S phase.
restriction point
Most cancers arise in _______ tissue from cells that have acquired a genetic change that leads to a selective growth advantage.
somatic
The two key families of proteins responsible for regulating the cell cycle are:
- cyclin-dependent kinases
2. cyclins
The two families of CDK inhibitors include:
- INK4 family
2. CIP/Kip family
What happens when anti-proliferation genes are mutated?
Cell is released from the normal proliferation constraints and divides as a cancer cell.
What mode of inheritance are mutations in anti-proliferation genes (also known as Tumor Suppressor Genes)?
recessive
What mode of inheritance are mutations in oncogenes?
dominant
Oncogenes are abnormally expressed or mutated forms of:
corresponding NORMAL CELLULAR proto-oncogenes
Tumor suppressor genes are also known as:
anti-proliferation genes
The most important cell-cycle checkpoints are found at what 3 timepoints:
- G1/S
- G2/M
- M
Proto-oncogenes may be integrated into a viral genome and are expressed at ________ levels than their cellular counterparts under the control of the viral promoter.
higher levels
Tumor suppressor genes can cause cancer, but what must happen in the cell before it transforms to a cancerous state?
Both functional copies of the gene must be lost
Proto-oncogenes may encode proteins that differ in structure and function from their normal cellular counterparts. What are 3 general reasons for this?
- Mutations - premature truncation of protein or altered Amino Acid sequence
- Fusion/translocation - form hybrid protein
- Amplification - produce higher grade tumors
In breast cancer, Her2 _________ are associated with a higher grade tumor.
amplification
An important mechanism in TSG silencing is _________ of their promoters.
methylation
The function of the Rb protein is primarily to:
restrict cell growth
The Rb protein is regulated by:
phosphorylation
The hypophosphorylated form of Rb protein binds E2F, a ____________ required for cell cycle entry, then does what?
binds to E2F transcription factor and prevents its entry
______ is a tumor suppressor encoded by the TP53 gene that is altered/mutated in a majority of cancers.
p53 protein
p53 is normally induced by:
DNA damage and cell stress
Cells with a mutant p53 protein:
- continue to replicate damaged DNA and
2. do not undergo apoptosis
p53 is regulated by ________ modification, which alters its stability and function.
post-translational
What is MDM2?
A oncogene that is a critical regular of p53 function; frequently amplified in sarcomas.
A 55 year old man with a 40-year history of cigarette smoking is diagnosed with adenocarcinoma of the lung. A biopsy reveals that the tumor has a mutation in p53 and Ras. Which of the following statements about the genetic changes involved in cancer development is most accurate?
a) Tumor suppressor genes and oncogenes undergo loss-of-function mutations.
b) Tumor suppressor genes and oncogenes undergo gain-of-function mutations.
c) Tumor suppressor genes undergo gain-of-function mutations and oncogenes undergo loss-of-function mutations
d) Tumor suppressor genes undergo loss-of-function mutations and oncogenes undergo gain-of-function mutations.
D. TSG: Loss of function
Oncogenes: Gain of function
Cyclins directly interact with:
A. pRB
B. Cyclin-dependent kinase inhibitors
C. Cyclin-dependent kinases
D. p53
C.
