Cancer 3

Question 1

What are the gatekeepers involved in cell cycle control?

Answer 1

p53, Rb and Nf1

Question 2

What are the “caretakers” involved in DNA repair?

Answer 2

BRCA1, BRCA2 and mismatch repair genes

Question 3

What is Knudson’s 2-hit hypothesis?

Answer 3

In order for a cell to become a tumor cell, both its genes must be “hit” / inactivated

Question 4

What are the epigenetic alterations that can occur to cells?

Answer 4

1. Inactivate TSGs

2. Activate oncogenes

Question 5

Roles of “oncomirs” and TS miRNA?

Answer 5

Oncomirs cause the degradation of mRNA, lowering the expression of TSGs

TS miRNA can become inactive, which activate the oncogenes that would normally be affected by TS miRNA

Question 6

Glioblastoma

Answer 6

100x expression of miR21, an mRNA

Most common brain tumor

Question 7

Inherited / hereditary vs sporadic cases

Answer 7

Hereditary = almost always bilateral and earlier onset is seen

Sporadic = usually unilateral and later onset

Question 8

Retinoblastoma

Answer 8

Mutation of Rb1

High risk of 2nd hit; high penetrance, but not complete

Question 9

Role of Rb1?

Answer 9

Sequesters E2F; without Rb, E2F would be active, and continue cell cycle proliferation

Question 10

Li-Fraumeni syndrome

Answer 10

Mutation of p53

Highly variable phenotype, depending on where the 2nd hit occurs

Question 11

Role of p53

Answer 11

Involved in DNA repair and the induction of apoptosis

If p53 has a loss of fxn, damaged cells survive and proliferate

Question 12

Neurofibromatosis Type I

Answer 12

Mutation of Nf1

Neurocutaneous and dermatologic lesions

Lisch nodules, cafe au lait spots, plexiform neurofibroma

Question 13

Role of Nf1?

Answer 13

Nf1 inactivates the Ras proto-oncogene by increasing the GTPase activity of Ras

Mutation in Nf1 leads to continuously active RAS, eventually causing growth and tumor formation

Question 14

Hereditary breast cancer

Answer 14

Mutation in BRCA 1 and BRCA 2

Question 15

Familial adenomatous polyposis (FAP)

Answer 15

Mutation in APC

Tons of polyps!

Question 16

Role of APC

Answer 16

Normally, APC is supposed to bind to beta-catenin, phosphorylating it for degradation

If BC is not phosphorylated, it translocates to the nucleus, binds TFs and activates MYC

Question 17

Wnt signalling pathway

Answer 17

Wnt binds to ‘frizzled’ and activates ‘dishevelled’

‘Dishevelled’ inhibits the APC complex

Inactive APC = BC phosph -> cell degradation
Active APC = no BC phosph -> cell proliferation

Question 18

HNPCC

Answer 18

Mutation: TGF beta 2 receptor

TGFb II receptor mutation is secondary to the mismatch repair defect!

Question 19

Role of PTEN? What happens if PTEN is lost?

Answer 19

PTEN inactivates PKB/AKT and promotes cell death

If PTEN is lost, the cell cycle is not arrested and there is no apoptosis

Question 20

Role of WT-1? What happens if WT-1 is lost?

Answer 20

WT-1 is involved in renal differentiation

Wilms tumor = peds kidney cx

Question 21

Xeroderma Pigmentosum

Answer 21

Defect in nucleotide excision repair (NER)

Absorption of UV light -> pyramidine dimers; increased risk of skin cx

Most common defect is excision endonuclease deficiency

Question 22

Ataxia Telangiectasia

Answer 22

Mutation of ATM

P/W cerebellar ataxia, oculocutaneous telangiectasia

Question 23

Bloom syndrome

Answer 23

Mutation of BLM (a DNA helicase)

Loss of fxn -> many chromosomal breaks

BLM prevents XS sister chromatid exchanges

Question 24

Werner syndrome

Answer 24

Mutation in WRN (a DNA helicase and exonuclease)

Involved in unwinding DNA and trimming damaged DNA; important for telomeres

Mutation results in defective homologous recombo and base excision repair

Question 25

Fanconi anemia

Answer 25

DNA repair defect

Defective interstrand cross-link repair

Multiple chromosomal breaks -> upper limb skeletal abnormalities, pancytopenia

Question 26

Human papilloma virus (HPV)

Answer 26

Oncogenes E6 and E7

E6 binds to and inhibits p53, preventing DNA repair

E7 binds to and inhibits Rb, allowing uncontrolled proliferation