Oncogenes and Tumour Suppressor Genes Flashcards Preview

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Flashcards in Oncogenes and Tumour Suppressor Genes Deck (35)
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1
Q

viral oncogenes (v-onc)

A

copy of normal cell genes (c-onc) incorporated into viral particles - identification

2
Q

discover cell oncogenes by

A

analysis transduced cell gene seq in acute transforming retroviruses (neu)
identification of preferred integration sites of retroviruses (wnt1 mice)
characterisation of chromosomal translocations (BCR-ABL)
characterisation of amplified DNA sequence (NYMC)
direct gene transfer experiments to assay for biological activity of cell transforming genes (NRAS)
whole genome sequencing

3
Q

oncogene detection by DNA transfection

A

NIH 3T3 cells used as recipient - immortal not cancerous
oncogenes cause - foci formation (loss contact inhibition)
growth in semi-solid medium (loss anchorage dependence)
morphological abnormalities
reduced serum requirement
increased saturation dependency

4
Q

Oncogenes control growth by

A

secreted growth factors/ligands (SIS)
cell surface receptors (ERBB)
Intracellular signal transduction (RAS, ABL)
DNA-binding nuclear proteins/transcription factors (MYC/JUN)
cell regulatory proteins (MDM2, CDK) MDM2 act on G1S - divide quicker

5
Q

Mechanism of oncogene activation

A

Point mutation
Amplification
Translocation/ rearrangement

6
Q

Point mutation oncogene

A

hyperactive version - qualitative
HRAS - bladder, lung, colon, melanoma
KIT - GI, stromal

7
Q

amplification oncogene

A

quantitative - multiple copies on chromosome
ERBB2 - breast, ovarian, gastric, colon
NYMC - neuroblastoma (child)

8
Q

translocation/rearrangement oncogene

A

IGH-MYC - burkitts lymphoma - low expression gene put in high expression region
BCR-ABL - chronic myelogenous leukaemia - new protein

9
Q

Oncogene point mutation RAS family

A

signal transduction - G-protein

HRAS, KRAS, NRAS

10
Q

HRAS

A

murine Harvey sarcoma virus

11
Q

KRAS

A

Murine Keirsten sarcoma virus

12
Q

NRAS

A

neurblastoma

13
Q

1) Oncogenic RAS - ligand bind receptor

A

GTP bind RAS - signal transmission

14
Q

2) RAS GTPase actvity

A

GTP–>GDP = inactive

15
Q

3) Mutations at amino acid residues (12, 13, 61) (GTP binding)

A

Reduced GTPase activity

16
Q

4) Reduced GTP activity

A

GTP degraded slower + excessive signalling

17
Q

MAPK/ RAS-RAF-MEK-ERK Pathway (cause)

A

oncogenes ERBB, PDGFR, RAS, RAF

18
Q

MAPK leads to cancer by

A

overexpression gene in nucleus –> pro-proliferation

—> metastasis

19
Q

Oncogene activation by amplification

A

ERBB2
MYC
MDM2

20
Q

Oncogene amplification ERBB2

A

Breast , ovarian carcinoma - tyrosine kinase receptor (cell signalling)

21
Q

Oncogene amplification MYC

A

breast carcinoma - transcription factor pro-proliferative/apoptotic genes

22
Q

Oncogene amplification MDM2

A

sarcomas - negative regulator of p53 pathway

23
Q

Amplified regions exist as

A
Homogenously staining regions (HSRs)
Double minutes (DMs)
24
Q

Homogenously Staining regions

A

insertions within normal chromosomes (continuous, in tandem)

25
Q

Double Minutes

A

small paired chromatin bodies separate from chromosomes, spliced out

26
Q

Amplicon

A

unit of amplified genetic material

27
Q

MYCN detection

A

2 probes one for centromere of chromosome 2 and one for MYCN (2p), amplified 10-500 fold 25% neuroblastoma

28
Q

Oncogene activation translocation (novel chimeric gene)

A

escapes normal regulation, abnormal and transforming - common in leukaemias and lymphomas, identify by cloning

29
Q

Philadelphia chromosome (CML)

A
9;22 translocation 
9 breakpoint in intron of ABL oncogene
joins 5' region ABL to 3' region BCR on 22
tyrosine kinase related to ABL
always switched on
30
Q

Tyrosine kinase inhibitor for translocation

A

competitive inhibitor to ATP, which phosphorylates tyrosine kinase
specific - less toxic

31
Q

Oncogene activation - translocation to active region

A

Burkitts lymphoma - EBV/mosquito etiology

MYC activation - overexpression

32
Q

MYC translocations

A
t(8;14) (q24-q32)
t(8;22) (q24-q11)
t(2;8) (p12-q24)
MYC placed close to IGH locus - expressed high in lymphoid
H - 14q32
K - 2p12
L- 22q11
33
Q

Burkitts lymphoma

A

place oncogene in actively transcribed chromatin in antibody producing B cells

34
Q

Burkitts lymphoma - not MYC exon 1

A

removal of control sequence - overexpression MYC

35
Q

Burkitts lymphoma translocation cause

A

error in V-D-J gene rearranegment