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Flashcards in Carcinogenesis 2 Deck (62)
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1

define darwinian evolution and clonal expansion of the intent mutant

clonal expansion of the initiating mutant, in order that it will acquires 2nd mutation.

2

define caretaker gene

maintain genetic stability by repairing damaged DNA and replication errors and controlling the accuracy of mitosis.

3

what feature of tumour cells can mutation in a caretaker gene cause

genetic instability.

4

what type of genes are caretaker and gate keeper genes

tumour suppressor genes

5

define gatekeeper gene

negative regulators of the cell cycle and proliferation.
positive regulators of apoptosis.
positive regulators of cell differentiation.

6

do both tumour suppressor genes have to be hit in order for inactivation

Yes.

7

how can the promoter region of tumour suppressor genes be inactivated

hypermethylation of the CpG islands.

8

define epigentic silencing

hypermethylation of the CpG islands (promoter region)

9

what is typically the cause of the 1st hit in tumour suppressor genes

single point mutation.

10

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.

11

what is the most common feature of tumour cells

aneuploidy- daughter cells have the wrong amount go chromosomes.

12

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.

13

what gene is involved in retinoblastoma and is it a gate keeper of caretaker

gatekeeper
RB1

14

what gene is involved in Li- Fraumeni and is it a gate keeper of caretaker

p53
gate keeper and care taker

15

what are the principal tumours in Li fraumeni

sarcomas and breast

16

what gene is involved in familial adenomatous polyposis and is it a gate keeper of caretaker

APC
Gate keeper

17

what are the principal tumours in familial adenomatous polyposis

colorectal

18

what gene is involved in familial breast cancer and is it a gate keeper of caretaker

BRAC1/BRAC2
caretaker

19

what are the principal tumours in familial breast cancer

breast and ovarian

20

what gene is involved in hereditary non polyposis colorectal cancer and is it a gate keeper of caretaker

hMLH1, hMSH2
care taker

21

what are the principal tumours in hereditary non polyposis colorectal cancer

colon endometerial

22

define proto-oncogenes

promote cell proliferation, survival, angiogenesis and negative regulation of apoptosis

23

define oncogenes

mutations lead to activated versions or increased expression of proto-oncogenes – GAIN OF FUNCTION

24

how many mutant oncogene do you need to induce gain of function

one- the mutated gene is dominant.

25

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.

26

what is the minimum number of genetic alternations required to transform a normal cell into a neoplastic cell

3

27

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.

28

do tumour cells require a stimulus of positive growth factor before they enter the cell cycle and divide

NO

29

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

30

what factors carries signals about whether a cell needs to enter the cell cycle or not

growth factor