Lecture 48 + DLA 32 Flashcards Preview

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Flashcards in Lecture 48 + DLA 32 Deck (31)
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1

What does a mutation in the RB lead to?

retinoblastoma and osteosarcoma

2

What does a mutation in the TP53 gene lead to?

Li-fraumenti syndrome

3

what does a mutation in the APC gene lead to?

familial adenomatous polyposis (colorectal cancer)

4

What does a mutation in the MSH2, MLH1, and PMS1/2 genes do?

Hereditary nonpolyposis colon cancer (HNPCC)

colorectal cancer

5

BRCA1/2 mutation?

familial breast or ovarian cancer

6

NF1 mutation?

Neurofibromatosis 1

7

WT1 mutation?

wilm's tumor

8

how does wilms tumor occur?

it is an autosomal dominant inheritance pattern

loss of function of the WT1 gene (chromosome 11), thus incontrollable growth and differentiation

9

What is the two hit hypothesis for sporadic cancer?

mutations of both tumor suppressor genes must occur before cancer can develop

10

What is the two hit hypothesis for familial cancer?

The first mutation is inherited, thus the second mutation can occur in any cell.

11

What does the second mutation lead to?

loss of heterozygosity

12

What mechanisms can lead to the second mutation or second hit?

1. loss through non-disjunction

2. mitotic recombination

3. gene deletion

4. point mutation

13

What is the regulatory protein of the G1/S checkpoint?

Rb protein

14

what is the G1/S checkpoint pathway?

1. growth factor presence leads to the creation of the cyclin/cdk complex

2. cyclin/cdk phosphorylate Rb

3. Rb then no longer represses E2F

4. E2F then activates S-phase genes

no cyclin/cdk complex = no cell division

15

What does a mutation in the Rb protein do?

It does not bind to the E2F protein, thus their is an increase in s-phase genes and unregulated cell division

16

What does familial cancers look like on a pedigree?

seen in all generations
due to dominant traits

17

What is the diff between familial and sporadic retinoblastoma?

familial:
multiple tumors
bilateral
early onset

sporadic:
single tumor
unilateral
later onset

18

What are the three functions of the P53 protein?

1. regulate the cell cycle (proliferation)

2. scan the DNA for errors

3. apoptosis

19

What does p53 increase the expression of?

increases the expression of proteins that lead to apoptosis

20

The normal APC pathway?

APC is a component of the WNT signaling pathway

1. destruction of complex inactivated
2. beta-catenin not degraded
3. beta-catenin moves to the nucleus and forms with TCF-4
4. activates growth promoting genes

when there is no Wnt signal beta-catenin is degraded

21

what happens when APC is mutated?

Beta-catenin is never degraded even in the absence of the wnt signal.

thus growth is occuring without the wnt signal

22

FAP vs HNPCC

FAP:
APC mutation
accelerated
numerous polyps
normal tumor progression
gatekeeper

HNPCC:
MSH2 / MLH1 mutation
normal tumor initiation
fewer polyps
accelerated tumor progression (microsatellite instability)
caretaker

23

explain BRCA1 and BRCA2

involved in DNA repair and apoptosis

allelic heterogenicity is relevant here

usually leads to breast and or ovarian cancer when mutated

24

what are the epigenetic chances in tumor cells?

tumor suppressor genes are methylated and deactivated

DNA methylation and histone modifications

25

miRNA's in cancer cells?

more miRNA's that inhibit tumor suppressor RNA's

reduction of miRNA's that could inhibit oncogene RNA

26

roles of epigenetics in tumorigenesis?

Silencing of tumor suppressor loci causing cell
overgrowth

Loss of imprinting causing activation of growth
associated genes or oncogenes

MicroRNAs

27

What is an intrinsic pathway of apoptosis?

1. BAX is produced due to DNA damage
2. BAX goes to the mito
3. BAX leads to the release of cytochrome C from the Mito and activates apaf-1
4. Cleavage of procaspases to caspase proteases (activation via a cascade)
5. apoptosis

28

what does the BCL protein do?

inhibits the action of BAX, thus non-apoptotic

29

what three things trigger apoptosis?

1. lack of supply of growth factor (extrinsic pathway)

2. response to genotoxic stress (intrinsic pathway)

3. mediated by immune cells (perforin/granzyme pathway)

30

extrinsic pathway of apoptosis?

1. binding to death receptor

2. adaptors

3. disc formation

4. caspase 8 activation

5. execution pathway