Cancer Genetics Flashcards Preview

Developmental Genetics > Cancer Genetics > Flashcards

Flashcards in Cancer Genetics Deck (39):
1

What is the difference between sporadic and familial cancers?

Sporadic - one cell carries the mutation.
Familial - all cells carry one mutation.

2

What is the probably of second mutations for both sporadic and familial cancer?

Familial - nu.
Sporadic - u.

3

Define Dysplasia.

The enlargement of an organ or tissue by the proliferation of cells of an abnormal type.

4

Define Neoplastic. (Neoplasm).

a new and abnormal growth of tissue in a part of the body, especially as a characteristic of cancer.

5

Define metastasis

Dissemination of cancer, often to novel tissue.

6

What are the three types of cancer?

Carcinoma - Cancer of epithelial origin.
Leukemias and lymphomas - Originate from cells of the bone marrow.
- Leukemia - disseminated.
- Lymphomas - similar to Leukemia but restricted to lymph nodes.
Sarcoma - Connective tissue cancer.

7

What are the three types of cancer cell lines useful for cancer research?

Normal - ceases after 50 cycles.
Immortal - Cancer screening.
Cancerous - from tumour itself.

Many cell lines are homogenous -> not representative of tumours.

8

Real cancers start out clonal.
True or False?

True, but don't remain that way

9

What are athymic mice and their use?

Nude mice, unable to reject tissue so allows for the growth of human cancer cells, which can undergo assay for in vivo effect.

10

What are KM12C and KM12SM?

Primary colon cancer cells from patient.

KM12C derived from cells are primary tumour site.
KM12M - derived from secondary metastasis.

11

Why are metastasized cells usually genetically different?

Genomic instability -> aneuploid.

12

Typically cancer cells exhibit:

Early - Minor increase in cell number
Hyperplasia - Major increase in cell number
Dysplasia - Disrupted normal cell population and organ function.
Invasion - Cancer cells invade another tissue.

13

Describe cancer cell evolution.

- Progressive mutations.
- Give new property. e.g loss of contact inhibition -> metastases.

14

What do mutations that cause cancer often effect?

- Cell cycle genes. (Loss of repressive control -> increased proliferation -> more cells = more mutations
- Apoptosis (DNA damaged cells -> more chance for mutations).

15

True or False?
Cell cycle checkpoints are often defective in cancer.

- p53.

16

Describe oncogenes.

- Increase activity to promote cancers.
- GOF mutations or Loss of repressor.
- Proto-oncogenes = non mut versions.
- Dominant effect.

17

Do oncogenes have a dominant or recessive effect?

Dominant effect, only require one mut allele.

18

Describe tumour suppressor genes.

- Activity typically inhibits events leading to cancer.
- Roles in checkpoints, apoptosis, genome stability.
- LOF in both alleles (recessive effect)

19

Do TSGs have dominant or recessive effect?

Recessive effect.

20

How can DNA viruses turn on oncogenes?

Viral genome integrates into host chromosome, which contains genes that activate cell proliferation.
e.g T antigen from SV40.
- Rare

21

How can retroviruses turn on oncogenes.

Transformation of cells, one of the three RV genes replaced by an oncogene, resulting in its expression.

22

Describe the NIH3T3 transformation assay.

NIH3T3 transformation assay
- mouse NIH3T3 cells have some but not all properties of cancer cells (immortal but exhibit contact inhibition of growth)
- NIH3T3 cells + human cancer cell DNA can gain cancer cell properties (relief from contact inhibition of growth)
monolayer >>> colonies of transformed cells (foci)
- screen transformed mouse NIH3T3 cells for human DNA (by Alu repeats) -> identify the activated oncogene.

23

Describe contact inhibition

Contact inhibition is a regulatory mechanism that functions to keep cells growing into a layer one cell thick (a monolayer). If a cell has plenty of available substrate space, it replicates rapidly and moves freely.

24

Oncogene mutations can ___ the protein or cause ____ to be made.

activate (v-RAS) // more (gene amplification)

25

What are some of the known roles of proto-oncogenes.

- secreted growth factors
- cell surface receptors
- signal transduction pathways
- DNA binding transcription factors
- regulators of cell-cycle progression

26

Amplification can turn on proto-oncogenes, Describe and give an example of amplification resulting in cancer.

Amplification (eg ERBB2 [EGF receptor] in breast cancer)
- increasing the gene copy number is common
- can be intra-chromosome amplifications
(HSRs ‒ homogenously staining regions)
- or extra-chromosomal amplifications
(additional small chromosomes ‒ double minutes)
- oncogenes in these amplifications contribute to cancer
(increased gene product)
- amplification also contributes to drug resistance during chemotherapy

27

What is the breakage-fusion-bridge model of intrachromosomal DNA amplification?

Slide 32

28

How can genomic instability in cancer cells manifest?

- MMR.

29

True or False
~45% of MIN+ tumours lost TGF signalling.

False, 90%.

30

What are the likely candidates in CIN?

chromosome condensation
centromere and kinetochore function
spindle checkpoints (chromatid separation)
DNA damage repair/checkpoints

31

True or False?
Several syndromes have breast cancer as a symptom.

True. Li Fraumeni, and ATM.

32

True or False?
BRCA1 and BRCA2 have different pathways but cause similar outcomes.

True

33

With an example describe the activation of a proto-oncogene with a point mutation.

- H-RAS1.
- Ras signals from growth factor receptors (EGFR), which binds GTP to activate Ras.
- Ras has GTPase activity, leading to growth, proliferation and differentiation.
- Active Ras-GTP becomes inactivate Ras-GDP.
- Point mutation decreases GTPase activity, by being unable to inactivate it. Prolonging Ras-GTP and its growth signalling.
- Common in cancers.

34

With an example describe the activation of a proto-oncogene via chromosomal translocation.

- Chromosome instabilty is common, but random.
- t(9,22) translocation = Philadelphia chromosome (chronic myeloid leukemia).
- Translocation creates a fusion protein, which constitutively activates tyrosine kinase, a growth signal.

35

How have tumour suppressors been identified by?

1. Positional cloning of rare familial cancer genes
2. Identification of cancer genes found in commonly deleted
regions of human chromosomes (loss-of-heterozygosity)
3. Screening for cancer mutations in cell cycle genes

36

Describe the Knudsens two hit hypothesis with the Rb gene.

- Two mutations, one in each allele required for loss of TSG function..
- In familial cancers one mutant allele is inherited.
- Point mutation.

37

How is a second allele mutated in TSGs?

- Point mut.
- Gene conversion
- Loss of chromosome.
- Deletion of part of chromosome.

38

What is LOH?

- Other allele/chromosome has been deleted/replaced.

39

How do you locate TSG by LOH?

Genetic markers.
If missing, thats the area of LOH.
Overlap results with other individuals, and area of overlap is where TSG is located.