Bchem Block 3 Cancer

Front 1

4 oncogenes

Back 1

ErbB receptor family (GH receptors)
Ras (GTPase)
ERK (kinases)
c-Myc (transcription factor)

Front 2

2 ErbB family members

Back 2

(1) Epidermal growth factor receptor 1: EGFR and Erb-1
(2) Human epidermal growth factor 2: Her2 and Erb-2

Front 3

disease associated with EGFR (Erb1) mutations?

Back 3

never smoker lung cancer

Front 4

disease associated with Her2 mutation?

Back 4

aggressive breast cancer

glioblastoma multiform

Front 5

how many of all human cancers have oncogenic Ras?

Back 5

20-30%

Front 6

% of colon cancers with oncogenic Ras?

Back 6

40%

Front 7

what disease associated with ERK pathway mutations?

Back 7

melanoma

Front 8

how does normal Myc work?

Back 8

recruits histone acetyltransferase to increase gene expression by unwinding DNA

Front 9

disease assoicated with c-Myc oncogene?

Back 9

Burkitt's lymphoma

Front 10

4 types of caretaker genes

Back 10

(1) ds DNA break repair
(2) Base excision repair
(3) Nucleotide excision repair
(4) Mis match repair

Front 11

2 dsDNA break repair genes?

Back 11

(1) CHK2
(2) BRCA (1 and 2)

Front 12

base excision repair gene example?

Back 12

MYH gene

Front 13

disease associated with MYH mutation?

Back 13

colorectal cancer

familial adenomatous polyposis (FAP), when APC is also mutated

Front 14

what gene, when mutated, has high penetrance to cause adenomas and cancers (>90%)

Back 14

APC (often precipitated by mutation in MYH)

Front 15

cause of xeroderma pigmentosum?

Back 15

defect in nucleotide excision repair (a caretaker gene function)

Front 16

2 examples of mis match repair caretaker genes?

Back 16

MSH 2

MLH 1

Front 17

what does mismatch repair failure lead to?

Back 17

microsatellite instability (MSI)

Front 18

what causes Lynch syndrome?

Back 18

Mutations in mis-match repair genes, leading to MSI:
60 % = mutations to MSH2
30% = mutations to MLH1

Front 19

2 types of gatekeeper genes?

Back 19

(1) Rb
(2) p53

Front 20

describe normal function of Rb

Back 20

* Hypophosphorylated Rb = tumor suppressor that reduces cellular proliferation by binding E2F
* Hyperphosphorylated Rb = stimulates cell cycle because E2F is free to interact with cyclin and stimulate CDK2 to start S phase.

Front 21

what is the role of E2F in tumor suppression?

Back 21

hypophosphorylated Rb binds E2F, preventing it from interacting with Cyclin E. Cyclin E cannot therefore lead to activation of CDK2. S-phase is therefore inhibited

Front 22

what mutations account for 90% of small cell lung cancers?

Back 22

Rb mutations

Front 23

what mutations account for 20-25% of bladder cancer?

Back 23

Rb mutations

Front 24

what mutation accounts for 30% of liver cancers?

Back 24

Rb mutations

Front 25

what type of mutations generally occur in p53?

Back 25

missense mutations

Front 26

% of human cancers that have mutations in p53?

Back 26

50%

Front 27

% of non-melanoma skin cancers that have p53 mutations?

Back 27

80%

Front 28

what syndrome is caused by inherited p53 mutation?

Back 28

Li-Fraumeni

Front 29

inheritance of Li-fraumini?

Back 29

autosomal dominant

Front 30

characteristics of Li-Fraumini?

Back 30

* Breast cancer, often before age of 50
* Soft tissue sarcomas
* Osteosarcomas
* Brain tumors

Front 31

how does HPV virus interact with the 2 gatekeeper genes?

Back 31

HPV virus produces E6 and E7

E6 binds p53 and leads to its destruction
E7 binds Rb and inhibits its normal function by preventing its interaction with E2F

Therefore HPV causes proliferation, and then prevents induction of apoptosis

Front 32

what condition/disease would cause multiple primary cancers, tumor site predominantly in proximal colon, and extracolonic cancers like bile duct cancer and sebaceous cell cancers?

Back 32

Lynch Syndrome, due to MSH2 or MLH1 mutations (mismatch repair caretaker genes)