Identification of inherited cancer-causing genes Flashcards
(31 cards)
What are oncogenes?
Genes that, when mutated or expressed at high levels, can lead to cancer by promoting cell growth and division.
What is the primary challenge in identifying tumor suppressor genes?
They have a primarily recessive phenotype at the cellular level, requiring dominant expression methods for identification.
What is linkage analysis?
A method using polymorphic markers to identify chromosomal segments bearing cancer-causing mutations in hereditary cancer.
How do inherited tumor suppressor mutations typically manifest?
They result in individuals who are heterozygous for the mutation in all cells but require two hits for tumor formation.
What does loss of heterozygosity (LOH) indicate in tumor DNA?
It suggests that a normal tumor suppressor gene and surrounding polymorphic markers have been lost.
What is a genome-wide association study (GWAS)?
A study comparing SNP frequencies between cases and matched controls to identify genetic variants contributing to cancer susceptibility.
What are driver genes?
Genes that confer a growth advantage to tumor cells, directly contributing to cancer.
What are passenger genes?
Genes that undergo somatic mutations during tumorigenesis but do not confer a growth advantage.
What is the NF1 gene associated with?
Neurofibromatosis Type 1, a genetic disorder characterized by the growth of tumors along nerves.
What role does the NF1 gene product, neurofibromin, play?
It down-regulates RAS, a protein that transmits positive growth signals.
What is the significance of the TP53 gene?
It is the most commonly altered cancer-causing gene, with mutations found in more than half of all human tumors.
What is the function of the p53 protein?
It acts as a transcription factor regulating genes that affect cell growth, proliferation, and survival, especially in response to DNA damage.
What happens when TP53 is mutated?
Cells can evade DNA repair and apoptosis, leading to uncontrolled replication and tumor formation.
What are epigenetic changes?
Alterations in gene expression or phenotype caused by mechanisms other than changes in DNA sequences.
How can epigenetic alterations affect cancer development?
They can lead to abnormal gene silencing and activation of oncogenes, contributing to tumor progression.
What type of mutations are commonly found in the TP53 gene?
Somatic mutations, particularly in the DNA-binding domain.
What is the role of p21 in cell cycle regulation?
It blocks the inactivation of pRb, halting the cell cycle in the G1 phase to allow DNA repair.
What are the consequences of hypomethylation in tumor cells?
Increased activity of oncogenes and chromosomal instability.
What type of studies have been used to identify cancer-causing genes?
- Linkage analysis
- Loss of heterozygosity analysis
- GWAS
- DNA sequencing
What is a common effect of dietary carcinogens on the TP53 gene?
Induction of specific mutations that can lead to cancer.
What can continued replication of damaged DNA lead to?
Tumor formation
This occurs when components of cell cycle control are compromised.
Which DNA tumor virus is responsible for most cases of cervical cancer?
Human papilloma virus (HPV)
HPV inactivates both pRb and p53, preventing DNA repair and apoptosis.
What is Lynch syndrome also known as?
Hereditary nonpolyposis colorectal cancer (HNPCC)
Lynch syndrome accounts for 2% to 5% of colorectal cancer cases.
What is the lifetime risk of colorectal cancer for individuals with Lynch syndrome?
50% to 80%
This risk is particularly high for heterozygotes.
