Cancer 3 Flashcards Preview

MCB 2 > Cancer 3 > Flashcards

Flashcards in Cancer 3 Deck (26):
1

What are the gatekeepers involved in cell cycle control?

p53, Rb and Nf1

2

What are the "caretakers" involved in DNA repair?

BRCA1, BRCA2 and mismatch repair genes

3

What is Knudson's 2-hit hypothesis?

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

4

What are the epigenetic alterations that can occur to cells?

1. Inactivate TSGs
2. Activate oncogenes

5

Roles of "oncomirs" and TS miRNA?

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

6

Glioblastoma

100x expression of miR21, an mRNA

Most common brain tumor

7

Inherited / hereditary vs sporadic cases

Hereditary = almost always bilateral and earlier onset is seen

Sporadic = usually unilateral and later onset

8

Retinoblastoma

Mutation of Rb1

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

9

Role of Rb1?

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

10

Li-Fraumeni syndrome

Mutation of p53

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

11

Role of p53

Involved in DNA repair and the induction of apoptosis

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

12

Neurofibromatosis Type I

Mutation of Nf1

Neurocutaneous and dermatologic lesions

Lisch nodules, cafe au lait spots, plexiform neurofibroma

13

Role of Nf1?

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

14

Hereditary breast cancer

Mutation in BRCA 1 and BRCA 2

15

Familial adenomatous polyposis (FAP)

Mutation in APC

Tons of polyps!

16

Role of APC

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

17

Wnt signalling pathway

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

18

HNPCC

Mutation: TGF beta 2 receptor

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

19

Role of PTEN? What happens if PTEN is lost?

PTEN inactivates PKB/AKT and promotes cell death

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

20

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

WT-1 is involved in renal differentiation

Wilms tumor = peds kidney cx

21

Xeroderma Pigmentosum

Defect in nucleotide excision repair (NER)

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

Most common defect is excision endonuclease deficiency

22

Ataxia Telangiectasia

Mutation of ATM

P/W cerebellar ataxia, oculocutaneous telangiectasia

23

Bloom syndrome

Mutation of BLM (a DNA helicase)

Loss of fxn -> many chromosomal breaks

BLM prevents XS sister chromatid exchanges

24

Werner syndrome

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

25

Fanconi anemia

DNA repair defect

Defective interstrand cross-link repair

Multiple chromosomal breaks -> upper limb skeletal abnormalities, pancytopenia

26

Human papilloma virus (HPV)

Oncogenes E6 and E7

E6 binds to and inhibits p53, preventing DNA repair

E7 binds to and inhibits Rb, allowing uncontrolled proliferation