Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CMOD Block 2 > Four Letter Words and Cancer > Flashcards

Four Letter Words and Cancer Flashcards

1
Q

What oncogene is amplified in neuroblastoma?

A

NMYC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What tumor suppressor genes are mutated in Breast cancer?

A

BRCA1 and BRCA2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

If you have a BCR-ABL fusion gene being expressed, what type of cancer do you have?

A

Chronic Myeloid Leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Is the BCR-ABL fusion protein a passenger mutation or a driver mutation? What do those terms mean anyway?

A

It’s a DRIVER mutation because it contributes to the neoplastic process and is present in ALL CASES of chronic myelogenous leukemia. (doesn’t have to be in all…. but it has to contribute to the neoplastic process)

A passenger mutation is a mutation in the non-coding sequence that doesn’t contribute to the cancer phenotype.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is anaplasia?

A

Complete lack of cell differentiation.

“I do what I want” - giant cells, hyper chromatic nuclei, pleomorphism, mitoses….

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Dysplasia is what?

A

Disorderly but non-neoplastic cell proliferation ; specifically,

A LOSS IN THE UNIFORMITY OF INDIVIDUAL CELLS AND THEIR ARCHITECTURAL ORIENTATION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Lymphatic spread is typical of what type of cancers?

A

Carcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Hematogenous spread is typical of what type of cancers?

A

Sarcomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What’s the most commonly seen karyotypic abnormality in cancers? Second most?

A

Balanced Translocations followed by chromosomal deletions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Over-amplification of _______ is seen in Neuroblastoma, and can be seen in a karyotype as……

A

NMYC - overexpression scan be detected by the presence of DOUBLE MINUTES (extrachromosomal DNA elements) or HOMOGENEOUSLY STAINING REGIONS (integrated into a chromosome)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Carcinomas arise from what tissues?

A

Epithelial cells - GI, skin, Bronchial epithelium, etc….

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Sarcomas are derived from what type of tissue?

A

Mesenchymal: Connective tissue, bone, and cartilage. ….also fat.

Fibrosarcoma
Liposarcoma
Chondrosarcoma
Osteosarcoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Bronchogenic carcinomas generally metastasize to what areas?

A

Lung and Adrenals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

A balanced translocation between chromosomes 8 and 14 is the cause of 90% of what kind of cancer? What gene is malfunctioning?

A

Burkitt’s Lymphoma

Overexpression of MYC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

A reciprocal translocation leading to BCL2 over-expression is seen in __________________ (cancer type).

A

Follicular B-cell Lymphomas.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which is faster growing: Burkitt’s lymphoma or Follicular B cell Lymphomas?

A

Burkitt’s Lymphomas grow faster because they are the result of OVEREXPRESSION of oncogene MYC. Leads to continuous and accelerated cell proliferation.

Follicular B-Cell Lymphomas are slower growing because they are over expressing BCL2, the anti-apoptotic protein. The cells just continue to divide normally, but cannot die.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does MYC protein do?

A

TF - increases cellular production of CDKs and decreases production of CDKIs.

Leads to continuous cell proliferation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What mutation is present in Chronic Myelogenous Leukemia?

A

BCR-ABL fusion protein.

Reciprocal Translocation between Chromosomes 22 and 9.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Reciprocal translocation of chromosomes 14 and 18 lead to what type of cancer and over expression of what?

A

BCL2 overexpression in FOLLICULAR B-CELL LYMPHOMA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

The BCR-ABL fusion protein has constitutive____________.

A

Tyrosine Kinase activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

If you have a TMPRSS-ETS fusion gene what cancer do you have?

A

Prostate cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Rearrangement of HMGA2 is found in what type of cancer?

A

Pleomorphic carcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

13q14 deletion involves what gene?

A

Rb - tumor suppressor gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

A Chromosome 17 p deletion leads to loss of what tumor suppressor gene product?

A

Gene mutated = TP53

p53

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

NMYC (not MYC… different) is AMPLIFIED in what type of cancer?

A

Neuroblastoma (generally a child’s cancer)

NMYC (NeuroblastomaMYC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What gene is amplified in 20% of breast cancers?

A

HER2/NEU

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

CDKN2A is epigenetically mutated in what type of cancer mainly?

A

Pancreatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Glioblastomas express what?

A

PDGF and PDGFR - self-stustained growth!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What kinds of cancers make TGF-alpha and its receptor?

A

Sarcomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Other than the simultaneous expression of a receptor and its stimulatory ligand, what is another way that cancer cells gain autonomy in growth signals?

A

Induction of the Stromal Cells by the tumor cells. Spurred by signals from the parenchymal tumor cells, stromal cells secrete growth factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What binds to the ERBB1 receptor?

A

EGF

32
Q

What type of cancers over express EGF receptor ERBB1?

A

80% of squamous cell lung cancer

50% Glioblastomas

80-100% Head and Neck cancers

33
Q

What is the most commonly mutated pro to-oncogene?

A

RAS

34
Q

What are the other commonly mutated components of the RAS signaling pathway?

A

RAF, MEK, and ERK

35
Q

Where is RAS usually mutated? What kind of mutation?

A

RAS is mutated in the GTP hydrolyzing site with a point mutation. This makes RAS hold onto GTP, unable to hydrolyze it.

Constitutively active RAS.

36
Q

What was the non-receptor associated Tyrosine Kinase that we studied?

A

ABL

37
Q

What cancer does Imatinib treat?

A

Chronic Myelogenous Leukemia

BCR-AVL fusion gene = constitutive tyrosine kinase activity

38
Q

p21 is what kind of regulatory protein?

A

CDKI

39
Q

What is another name for p21?

A

CDKN1A

40
Q

What “guardian” protein causes up regulation of p21?

A

p53

41
Q

What proteins regulate cell cycle checkpoints?

A

CDKIs

42
Q

What are the CDKIs that regulate all the cyclin/CCK complexes?

A

p21 (CDKN1A), p27, and p57

43
Q

What are the CDKIs that inhibit only CDK4/CyclinD?

A

p16, p17, p18, p19

44
Q

CDKN2A does what in the cell cycle? What happens if it is lost?

A

CDKN2A is p16. p16 regulates CyclinD/CDK4 complex, that phosphorylates Rb.

If p16 is functional, it sequesters CyclinD/CDK4, so Rb is left in its Hypophosphorylated state. Rb is active, and can bind E2F, stalling the cell cycle to complete DNA repairs.

If p16 is deleted, CyclinD/CDK4 is free to phosphorylate Rb, leading to its inactivation. (Hyperphosphorylated state)

45
Q

Name the 4 most commonly mutated cell cycle regulatory proteins.

A

CDKN2A (p16)
CDK4
Cyclin D
Rb

They all affect Rb one way or another.

46
Q

Rb protein is lost in what cancer? what other cancers have Rb b=mutations?

A

Retinoblastoma

Breast cancer
SSLC
Bladder

47
Q

What checkpoint does Rb regulate?

A

G1–> S

48
Q

What is Rb’s function under normal circumstances.

A

Active Rb (hypophosphorylated) binds E2F, a TF responsible for Cyclin E synthesis. The cell cycle needs Cyclin E to progress, so it stalls, and waits for external mitogenic signaling to proceed.

Rb also recruits histone deacetylase and histone methyltransferase to block the promotors of E2F responsive genes.

When all is good to go ahead with the cell cycle, external mitogenic signals cause CyclinD and CDK4/6 up regulation. The complex of these two phosphorylates Rb, rendering it inactive.

E2F is able to go to the nucleus and cause transcription of Cyclin E, and the cell cycle can continue.

49
Q

Loss of what proteins would mimic the loss of Rb?

A

CDK4 or Cyclin D overexpression

CDKI loss (p21)

50
Q

HPV has what effect on Rb?

A

HPV codes a protein called E7 that binds to HYPOPHOSPHORYLATED (active) Rb.

51
Q

TP53 gene expression is triggered by….

A

Internal cell stress…..

Anoxia
Inappropriate RAS or MYC activity
DNA damage

52
Q

When cells aren’t distressed, what protein binds to p53?

A

MGM2 binds P53 and targets for destruction

53
Q

If you inherit a mutant TP53 allele, what is the condition called?

A

Li-Fraumeni syndrome –> 24-fold greater chance of getting tumors.

54
Q

How does p53 cause cells to enter quiescence?

A

Quiescence is like cell delay.

p53 initiates synthesis of p21 (CDKN1A) which inhibits cyclins/CDKs and allows Rb to remain active and phypophosphorylated, so it can sequester E2F.

p53 also upregulates DNA repair genes.

55
Q

Once DNA damage is repaired, how does p53 allow the cell to return to the cell cycle?

A

After all damage is repaired, p53 up regulates synthesis of MGM2, and destroys itself, essentially;

56
Q

How does p53 cause senescence?

A

Noone knows.

57
Q

How does p53 cause apoptosis?

A

Upregulation of BAX and PUMA

58
Q

What percentage of cancers have a defect in p53?

A

70%

59
Q

How does HPV affect p53?

A

HPV codes a protein called E6 that binds and sequesters p53.

(HBV and EBV also have proteins that do this)

60
Q

TGF-beta receptors dimerize upon ligand binding and cause what to occur?

A

Activation of CDKIs, and repression of growth promotors: Cyclins, CDKs, and MYC.

Pretty much does the opposite of MYC.
(remember, MYC down regulates CDKIs and up regulates cyclins and CDKs.

61
Q

What’s the awkward named protein in the TGF-beta pathway that is commonly mutated in certain cancers?

A

SMAD

62
Q

The TGF-beta pathway is mutated in 100% of what type of cancer?

What’s the second most common cancer seen with TGF-beta PW mutations?

A

PANCREATIC - ALWAYS

and 83% of colon cancers.

63
Q

What molecule mediates contact inhibition?

A

E-cadherin

64
Q

APC mutations are commonly seen in what type of cancer?

A

Sporadic Colon Cancers

Adenomatous Polyposis Coli

65
Q

What is APC’s job? What happens if it’s mutated?

A

APC binds to intracellular B-catenin, preventing it from going to the nucleus and up regulating transcription of proliferative genes.

WNT binds its extracellular receptor and APC lets go, under normal circumstances.

If APC is mutated, B-catenin is allowed to go to the nucleus even in the absence of WNT, causing uninhibited cell proliferation.

66
Q

Fas-FasL binding leads to the activation of….

A

Caspase 8

67
Q

BAX and BAK do what?

A

They’re pro-apoptotic proteins, and promote mitochondrial permeability so it will release cytochrome C.

68
Q

What is the function of BAD, BID, and PUMA?

A

They are BH3 proteins that neutralize the protective action of BCL2 and BCLXl.

When the sum of all the apoptotic promoting proteins is greater than the sum of those that prevent apoptosis, BAX and BAK are activated and mitochondrial permeability is induced.

69
Q

How does p53 use BH3 proteins as a protective mechanism against cell proliferation?

A

Under extreme circumstances of DNA damage, p53 up regulates the synthesis of BAX and PUMA, tipping the scales in favor of apoptosis.

Prevents replication of damaged cell.

70
Q

80% of B cell lymphomas have a mutation in what gene, that prevents apoptosis?

A

BCL2. The scales cant’ be tipped in favor of apoptosis if there is constitutively synthesized BCL2 going on. Protective mechanisms prevail, despite accumulation of DNA damage.

71
Q

At the end of 60-70 divisions, what can happen to cells?

A

They can enter senescence due to Rb and p53 action OR, in the absence of p53, can form DICENTRIC CHROMOSOMES as a last resort.

These are not able to separate at anaphase, and they break.

72
Q

In order for cells with dicentric chromosomes to avoid mitotic catastrophe and become neoplastic, what has to occur?

A

Telomerase reactivation.

73
Q

What protein does p53 induce to prevent angiogenesis?

A

TSP-1

74
Q

What protein induces the formation of new blood vessels?

A

VEGF

75
Q

What is the function of VHL?

A

VHL binds to HIF-1a and prevents it from going into the nucleus and upregulating VEGF.

CMOD Block 2 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions