Flashcards in Carcinogenesis 2 Deck (62)
define darwinian evolution and clonal expansion of the intent mutant
clonal expansion of the initiating mutant, in order that it will acquires 2nd mutation.
define caretaker gene
maintain genetic stability by repairing damaged DNA and replication errors and controlling the accuracy of mitosis.
what feature of tumour cells can mutation in a caretaker gene cause
what type of genes are caretaker and gate keeper genes
tumour suppressor genes
define gatekeeper gene
negative regulators of the cell cycle and proliferation.
positive regulators of apoptosis.
positive regulators of cell differentiation.
do both tumour suppressor genes have to be hit in order for inactivation
how can the promoter region of tumour suppressor genes be inactivated
hypermethylation of the CpG islands.
define epigentic silencing
hypermethylation of the CpG islands (promoter region)
what is typically the cause of the 1st hit in tumour suppressor genes
single point mutation.
what is typically the cause of the 2nd hit in tumour suppressor genes
chromosomal non-disjunction (leads to aneuploidy)
Chromosomal recombination- takes place in meiosis as it combines maternal and paternal genetic material. However in somatic cells during mitosis it can create a daughter cell that is homozygous for the first mutation in TSG.
what is the most common feature of tumour cells
aneuploidy- daughter cells have the wrong amount go chromosomes.
how do familial cancers predispose individuals with a greater risk of developing a cancer
inheritance of a mutant copy of a gatekeeper or caretaker gene, so only require 1 hit to be classes as cancer.
what gene is involved in retinoblastoma and is it a gate keeper of caretaker
what gene is involved in Li- Fraumeni and is it a gate keeper of caretaker
gate keeper and care taker
what are the principal tumours in Li fraumeni
sarcomas and breast
what gene is involved in familial adenomatous polyposis and is it a gate keeper of caretaker
what are the principal tumours in familial adenomatous polyposis
what gene is involved in familial breast cancer and is it a gate keeper of caretaker
what are the principal tumours in familial breast cancer
breast and ovarian
what gene is involved in hereditary non polyposis colorectal cancer and is it a gate keeper of caretaker
what are the principal tumours in hereditary non polyposis colorectal cancer
promote cell proliferation, survival, angiogenesis and negative regulation of apoptosis
mutations lead to activated versions or increased expression of proto-oncogenes – GAIN OF FUNCTION
how many mutant oncogene do you need to induce gain of function
one- the mutated gene is dominant.
what mechanisms activate oncogenes.
Translocation of a proto-oncogene from a low transcriptionally active site to an active site - aberrant expression of the oncogene.
E.g. moving the gene to where immunoglobulin’s are present as they are expressed transcpitionally a lot.
Point mutation - substitution of a single base pair can alter an amino acid in the protein causing it to become hyperactive
Amplification by insertion of multiple copies of an oncogene – increased expression.
what is the minimum number of genetic alternations required to transform a normal cell into a neoplastic cell
stage by stage tumorigenesis of colorectal cancer.
normal epithelium- loss of APC
Hyperplastic epithelium- DNA hypomethylation.
early (activation of K ras)- intermediate(loss of 18q TSG) - late adenomas
loss of p53- carcinoma
invasion and metastases.
do tumour cells require a stimulus of positive growth factor before they enter the cell cycle and divide
define signal transduction (process used to inform cells whether they need to enter the cell cycle )
passage of signals from outside the cell, through the almost impervious cell membrane, across the cytoplasm and into the nucleus, where changes in gene expression can take place