Cancer Genomics Flashcards Preview

General Systemic > Cancer Genomics > Flashcards

Flashcards in Cancer Genomics Deck (30):
1

What are the three classifications of germ line DNA changes?

VariantMutationPolymorphism

2

Define polymorphism

= variant not causing disease

3

Define mutation

= variant causing disease

4

Define variant

= any change from the reference DNA sequence

5

What are the three classifications of cancer DNA changes?

somatic mutation (variant)driver mutationpassenger mutation

6

Define somatic mutation (variant)

= any change from the patient's germ line DNA sequence

7

Define driver mutation

= somatic mutation contributing to cancer development

8

Define passenger mutation

= somatic mutation not contributing to cancer development

9

What are the small scale nucleotide sequence changes called?

Point mutationInsertion or deletion

10

What are the large scale nucleotide sequence changes called?

TranslocationAmplificationInsertion or deletion

11

What is the DNA change in epigenetic changes?

Promoter methylation

12

Genes involved in cancer are either..?

1. Oncogenes or 2. Tumour suppressor genes

13

What are oncogenes?

Gene function promotes cancer formationMutations causes increased gene functionMutations are dominant (only one allele mutated)

14

What are TSGs?

Gene function normally inhibits cancer formationMutations cause loss of gene function or expressionMutations are recessive (both alleles must be knocked out)

15

What is a driver mutation?

Driver mutation drive the tumour and contribute to cancer dvpmtInvolve oncogenes and TSGConfer advantage in growth or survival, therefore are positive selected(5-10 driver mutations per cancer?)

16

What are passenger mutations?

Mutations that do not confer any advantage (along for the ride) Just happens to be in the same cell as the driver mutations(1000-100,000 passenger mutations per cancer)

17

What is a driver mutation?

Driver mutation drive the tumour and contribute to cancer dvpmtInvolve oncogenes and TSGConfer advantage in growth or survival, therefore are positive selected(5-10 driver mutations per cancer?)

18

What is the MAPK signalling pathway in cancer?

Hallmark: sustained proliferative signallingKey genes: - EGFR (growth factor receptor)- HER2 (growth factor receptor)- (K)RAS- (B)RAF

19

What is HER2?

HER2 is a growth factor receptor which signals via the MAPK pathway (and other pathways)App. 20% of breast cancers have HER2 gene amplification i..e more growth factor receptors on the cell surface

20

Which drug targets the HER2 receptor in breast cancer?

Trastuzumab - monoclonal Ab that interferes with HER2 function and/or induces immune destruction of cells baring HER2*monoclonal Ab act on the cell surface

21

What is BRAF V600E?

BRAF is an important protein in the MAPK pathway.BRAF V600E is a mutation seen in 50% of melanomas that causes constitutive activation of MAPK signalling

22

Which drug targets V600E mutant BRAF?

Vemurafinib - small molecule inhibitor of V600E mutant BRAF*a small molecule inhibitor means that it acts in the cytoplasm

23

What is EGFR?

Growth factor receptor which signals via the MAPK pathway (and other pathways)15% of non-small cell lung cancers (NSCLC) have activating EGFR mutations

24

What drugs target EGFR?

Gefitinib and erlotinib: small molecule EGFR inhibitors

25

What is BRAF V600E? What disease is commonly associated with?

BRAF is an important protein in the MAPK pathway.BRAF V600E is a mutation seen in 50% of melanomas that causes constitutive activation of MAPK signalling

26

What is EGFR? What disease is commonly associated with this mutation?

Growth factor receptor which signals via the MAPK pathway (and other pathways)* 15% of non-small cell lung cancers (NSCLC) have activating EGFR mutations * EGFR is expressed in most colorectal cancers

27

What drugs target EGFR in non-small cell lung cancers?

Gefitinib and erlotinib: small molecule EGFR inhibitors

28

What drugs target EGFR in colorectal cancers?Which patient group does not respond to this drug?

Cetuximab: monoclonal Ab that inhibits EGFR function*patients who have tumours that have activating KRAS mutations DO NOT respond to cetuximab (even if they have EGFR) therefore must test

29

What is imatinib?

Inhibits multiple tyrosine kinases In: BCR-ABL fusion gene in CML and some ALL; CKIT in GI stromal tumours

30

What is sorafenib?

Inhibits RAF, VEGFR in hepatocellular carcinoma and renal cell carcinoma