20 Cancer Genetics Flashcards
What are the genetic aspects of cancer that allow it to be inherited?
Mutations must be in the germline to be inherited by the next generation
How spread amongst the cell population in an individual is inherited cancer?
Every cell will have a copy of the mutated gene
Explain Knudson’s two hit model
Explains retinoblastoma as an example. Requires two mutations for cancer. Runs bilaterally when inherited and unilaterally when both mutations are somatic/sporadic
What are three classes of cancer genes?
Tumor supressor genes - RB1, CDK inhib, controls cycling and prolif // oncogenes - Ras, enhances prolif when activated // DNA repair genes - BRCA2, maintains genome integrity
Explain the inheritance paradox
In mutations that increase cancer susceptibility, dominant inheritance patterns underly the recessive attributes of requiring two mutations at the cellular level
What are heterozygous loci and how do they help map cancer genes?
Set of markers at areas that constantly changes. Loss of markers along with tumorigenesis may indicate location of a tumor suppressor gene
What is the flow of steps to ID a gene’s role in cancer?
Examine large population pool > linkage study > ID specific anomalies via translocation map> interrupt gene and observe for results
What is the purpose of telomeres and what will occur in constitutively activated telomerase?
Telomeres limits number of replication, constantly activated telomerase will deregulate the number of replication cycles a cell can do
What causes neurofibromatosis, what type of gene is it? What is the intended purpose of the protein product?
Caused by mutation of NF-1 gene, a tumor suppressor that normally functions to down regulate Ras as a GTPase
What causes Li-Fraumeni, what type of gene is it? What is the intended purpose of the protein product?
Mutation of the p53 gene, a critical tumor suppressor that can sense DNA damage then bind to p21 to stop cell cycle as well as cause overly damaged cells to apoptose
What is characteristic of p53 mutations?
Multiple early age primary tumors
What gene is associated with Familial adenomatous polyposis coli? What type of gene is it? What type of tumor progression model does it follow?
APC is a suppressor gene and requires both copies to be lost for polyps to form. Even even with polyps, many other genes from other chromosomes need to be mutated to progress to cancer ie. K-RAS, p53, SMAD4
What genes are mutated in Hereditary non-polyposis colon cancer? What is the function of the original gene product? What other cancers can occur concurrently?
MSH2, MLH1 are DNA mismatch repair protein genes. Mutation rates can increase significantly with loss. Rectal, ovarian, bowel cancers also common
What are the differences between APC and HNPCC?
APC has a more polyps = odds of tumor progression
What are the two associated genes identified for breast cancer?
BRCA1/2
