Cancer - Tumor Suppressors And Oncogenes

Front 1

What are the 8 characteristics of a cancer cell?

Back 1

a. Disregard internal signals anti-growth…
b. avoid apoptosis…
c. avoid senescence and differentiation…
d. genetically unstable…
e. escape home tissue (invasive)…
f. Metastasis (survive and proliferate in foreing tissue.)…
g. sustained angiogenesis…
h. limitless replicative potential.

Hint 1

An LAUSD GAME

Front 2

How many mutations does an pro-oncogene need to become an oncogene?

Back 2

One allele (thus, it's a dominant effect)

Front 3

What type of gene (onco or TS) is NMyc?

Back 3

oncogene

Hint 3

None

Front 4

What type of mutation is seen in NMYC?

Back 4

Amplification, which leads to increased DNA, which leads to increased mRNA and increased protein

Hint 4

None

Front 5

What sort of tumor does NMYC cause?

Back 5

Neuroblasatoma

Front 6

With respect to cancer, what type of gene (TS or oncogene) would you worry about it being mutated to cause it to be constitutively active?

Back 6

oncogene

Front 7

What type of mutation is M4eo an example of?

Back 7

Oncogene: chromosome inversion of Flt3 (receptor tyrosine kinase) causing to be constitutively active [can also be caused by a point mutation]

Front 8

What clinical relevance is the chromosomal inversion of M4eo?

Back 8

WBC do not differentiate, which leads to Acute myologenous leukemia type 4 (with eosinophils)

Front 9

What are two possible outcomes of translocations? And why?

Back 9

overexpressed (due to new promoter) and missexpressed (novel protein)

Front 10

Give 2 general outcomes of Translocation (Hint: what happens in a translocation)

Back 10

fusion of proteins and switch to different promoter

Hint 10

None

Front 11

What type of translocation do these examples demonstrate? PML/RAR and Burkitt's Lymphoma.

Back 11

Fusion of 2 proteins-PMLRAR and Swith to different promoter- Burkitt's Lymphoma

Hint 11

None

Front 12

1. What pathogen is Burkitt's caused by? 2. What causes large B-cell lymphoma?

Back 12

1. Burkitt's is caused by the translocation a immunoglobin promoter of a being moved to a Myc gene.

2 Diffuse large B-Cell lymphoma is also caused by transocation of a promoter (TTF, PIM1, IgH) to the Bcl6 gene

Hint 12

None

Front 13

What type of mutation WBCs to get stuck in the promyolocytic stage, causing promyelocytic leukemia?

Back 13

fusion of proteins (RAR with PML)

Front 14

What does RAR stand for?

Back 14

Retinoic acid receptor

Front 15

Would the transcriptions of an mRNA transporter be considered an oncogene or a TS?

Back 15

oncogene: Overexpression

Front 16

What type of mutation is E14E? What type of tumor is this related to?

Back 16

abberant transport of mRNA out of the nucleus --> overexpression --> Solid tumor

Hint 16

None

Front 17

Match the following characteristic with either TS or oncogene: loss of function, misexpressed, only one mutated copy is needed, inherited, loss of apoptosis pathway, genomic instability, acts in dominant fashion, usually involved in growth, release cells from growth control, usually loss of both wild type genes

Back 17

TS: Loss of function, loss of both alleles, loss of apoptosis pathway, genomic instability, release cells from growth contorl… ONCOGENE: misexpressed, acts in dominant fashion, usually involved in growth, only one mutated allele is needed

Front 18

How do you inactivate a TS?

Back 18

mutations and hypermethylation

Hint 18

None

Front 19

What is associated with "loss of heterozygosity", TS or oncogene?

Back 19

TS now only one gene and that gene is mutated Loss of function

Front 20

With respect to tumor suppressor genes, what is dominant negative?

Back 20

when the product of one allele affects the normal function of the product of the other allele.

Front 21

Given a loss of one wild type allele at birth, name 5 ways a tumor suppressor gene can be inactivated.

Back 21

1) dominant negative, 2) Dominant active, 3) imprinted, 4) LOH, 5) mutation

Hint 21

AL MIND

Front 22

What are 6 ways to have a LOH?

Back 22

a) nondisjunction (chromosome loss)… b) nondisjunction and duplication… c) mitotic recombination… d) gene conversion… e) deletion… f) point mutation

Front 23

In tumor suppressor genes, what is the most common way for a person to lose the normal allele?

Back 23

LOH

Front 24

What type of gene TS or oncogene would methylation have an increased cancer risk?

Back 24

TS, since methylation silences a gene

Front 25

What are 2 causes of increased methylation of Tumor suppressor genes?

Back 25

a) aging and 2) chronic ulcerative collitis

Front 26

what are Rb, p16, p15, p14, p73, caspase-8, DAP kinase, E-cadherin, APC, Arf, and BRCA1 and 2?

Back 26

tumor suppressors

Front 27

Do tumor suppressors have to lose both alleles to be inactivated?

Back 27

no

Front 28

What is APC mutation associated with?

Back 28

FAP (APC is a tumor suppressor that gets truncated in FAP.. CRC)

Front 29

Which is related to inheritance, TS or oncogenes?

Back 29

TS

Front 30

what decade would you expect to find sporadic cancer and inherited cancer?

Back 30

Sporadic after 5th decade, and inherited 2nd and 3rd decade.

Front 31

Which chromosome is BRCA1 and BRCA2 found on ?

Back 31

BRCA1=chr 17… BRCA2=chr 13

Front 32

Which chromosome would you find APC gene on?

Back 32

5

Front 33

What chomosome would you find mismatch repair mutation (HNPCC)?

Back 33

2

Front 34

Match the gene with the CRC: FAP and HNPCC

Back 34

FAP: APC truncation… HNPCC: MSH2 and MLH1

Front 35

Which protein and cancer is the Wnt pathway impliated?

Back 35

APC truncation --> FAP

Front 36

What is the RET gene implicated in?

Back 36

Oncogene inheritance, which usually presents late in life with neoplasm of the endocrine system… seen also in sporadic

Front 37

1) What contribution do SNPs and haplotype blocks have in familial risk to cancer? 2) Which has a higher incidence in a population, high penetrance alleles like BRCA1 or SNP (haplotype blocks)?

Back 37

low (as compared to alleles like BRCA), 2) SNPs and haplotype blocks

Front 38

What significance do SNPs and haplotype block for patient care in the future?

Back 38

microarray predictors for cancer

Front 39

1) Match the following with either TS or oncogene… 2) which are transcription factors and which are signal transduction mediators?: Flt3, p53, Rb, AKT, RAS, Myc

Back 39

Transcription Factors: p52 (TS), Rb (TS), Myc (oncogene)… Signal transduction: Flt3 (TKR… oncogene), RAS (oncogene), AKT (oncogene)

Front 40

1) Put these in order to show which suppresses which… 2) state which are TS and which are oncogenes: Cyclin-D, Rb protein, p16

Back 40

p16 (TS) supresses cyclin D (oncogene), cyclin D suppresses Rb (TS)

Front 41

1) Put these in order to show which suppresses which… 2) state which are TS and which are oncogenes: ARF(p19), MDM2 and p53

Back 41

ARF-p19 (TS) suppresses MDM2 (oncogene), Mdm2 suppresses p53 (TS)

Hint 41

None

Front 42

What is the healthy response (non cancer) to an oncogene mutation?

Back 42

up regulation of one of the TS, like p53 or Rb… which leads to apoptosis or senescence

Front 43

What is the progression to cancer? What can cause these progressions?

Back 43

1) Normal –(1) --> Hyperproliferative –(2)--> early adenoma --> late adenoma --> carcinoma --> metastasis… 2) loss of TS or activation of an oncogene

Hint 43

MiCHAEL

Front 44

In terms of cancer, what effect does HPV have? (Hint: E7 and E6)

Back 44

HPV --> E7 --> suppresses Rb which will then allow expression of E2F1 (cell cycle promoting)… 2) HPv --> E6 --> suppresses p53, which will indirectly inhibit p21 and bax (TS)

Front 45

What histologic presentation does Promyelocytic leukemia have?

Back 45

blast promyelocytes with rods --> lead to bleeding by using up coagulation factors

Hint 45

None

Front 46

What does the fusion of the PML/RAR protein cause physiologically? What disease does this protein fusion cause? How is it treated?

Back 46

1) the retinoic acid receptor causes the the retinoic acid receptor to become less sensitive. 2) Acute promyelocytic leukemia… 3) retinoic acid (vit-A which drives the cells to neutrophils) and block the Flt3

Front 47

Besides the PML/RAR protein fusion, what 2nd hit is seen in mice with APL (acute promyelocytic leukemia)?

Back 47

Flt3 (tyrosine kinase receptor) mutation

Front 48

What does a flt3 mutation give a cell?

Back 48

survival advantage

Front 49

Which type of gene mutation (TS or oncogene) is likely to end in genetic instability?

Back 49

TS

Front 50

What is a good explanation for tumor resistance?

Back 50

tumors are heterogenic

Front 51

What are 4 methods for observing gene function in cells?

Back 51

cell lines with gain of function (oncogene)… cell lines with loss of function (TS)… RNAi (knock-down of gene expression)… Viral vectors (to transport a transcript for gain of function)