Brainscape's Knowledge GenomeTM

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


See full index

Genetics > Genetics of Cancer > Flashcards

Genetics of Cancer Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

tumor progression

A

normal -> hyperplastic –> dysplastic –> neoplastic (cells become immortal) –> metastatic

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

tumor progression results from waves of mutation followed by

A

clonal expansion

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

incidence of cancer increases exponentially with

A

age (5th to 6th power)

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

are cancers derived from a single cell

A

yes they are monoclonal - mutation increases with time

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

what strongly suggests that cancer cells are derived from a single cell

A

all cells from cancer have the same copy of the X inactivated

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

malignancy of B cell (produce antibody producing plasma cells)

A

multiple myeloma

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

all myeloma patients produce the same antibody molecule which is

A 
monoclonal Ig (M-spike)
proves monoclonality of cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

net cell growth in a healthy individual is what

A

cell birth = cell death

in cancer, cell birth > cell death

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

what are the cancer causing genes

A 
oncogenes (normally stimulates growth)
suppressor genes (normally inhibit growth)
repair genes (normally limit mutations)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

types of mutations in the cancer causing genes

A

proto-oncogene - gain of function mutation
tumor suppressor genes - loss of function
repair genes - increase frequency of mutations

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

MAP kinase pathway - cellular growth control

A
  1. growth factors
  2. growth factor receptor tyrosine kinase
  3. cytoplasmic receptor tyrosine kinase
  4. proteins with GTPase activity/cytosolic signal transducer
  5. DNA binding nuclear protein transcription factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

for cellular growth control, where do the instructions come from

A

outside of the cell (growth factors)

1 and 2 are extracellular
3 and 4 are cytoplasmic
5 on nucleus

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

regulates cell proliferation

A

proto-oncogenes <— mutation in it leads to oncogene

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

what happens when mutation of proto-oncogene

A

production of mutant protein that results that stimulates cell division or increased expression of a gene that leads to large amount of protein which stimulates cell division

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

how does MAP kinase cascade amplify signals

A

through geometric recruitment

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

what happens with the activation of kinases

A

phosphorylation of serine and threonine residues

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

how is tyrosine kinase receptor/growth receptor activated

A

ligand aka growth factors bind to the receptors which then dimerize and phosphorylate then there is further phosphorylation of tyrosine residues

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

how do you oncogenically activate a receptor

A

point mutation on the receptor (Val –>Gln) which changes a single amino acid making receptor constitutively active (Neu oncoprotein)

truncation/deletion - in absence of signal, receptors still dimerize and become constitutively active (ErbB oncoprotein)

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

oncogenic activation by translation aka illegitimate recombination

A 
Burkitt lymphoma (activation of myc)
chronic myeloid leukemia (activation of abl)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is myc

A

nuclear transcription factor (5) that is impo for G1/S transition and stimulates the cell cycle

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

mechanism in Burkitt lymphoma

A

recombination between chromosome 8 and 14 which puts myc (8) under the control of IgH promoter (14) now causing increased production of myc (usually made in small amounts) which leads to overstimulation of the cell cycle —> cancer

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

what fails to differentiate in Burkitt lymphoma

A

lymphocytes

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

another name for chronic myeloid leukemia

A

philadelphia chromosome 22

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

mechanism in chronic myeloid leukemia

A

recombination between chromosome 9 and 22 which makes a hybrid with abl (9) and bcr (22) genes fused together —> unregulated cystolic tyrosine kinase so abl is stuck in its active form not needing a signal to activate

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

what is abl

A

a cytoplasmic tyrosine kinase (3)

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

what can be used to block the bcr-abl hybrid

A

gleevec or imatinib mesylate (STI571)

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

mechanism of imatinib mesylate

A

it is a tyrosine kinase inhibitor so it binds to the bcr-abl hybrid active site and prevents its activity

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

A 52 year-old man with chronic myelogenous leukemia tests positive for the presence of the Philadelphia chromosome. How does this change the ABL proto- oncogene to an oncogene? This protein

A

constitutive kinase activity

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

what is Ras (4)

A

GTPase involved in major cell proliferative pathway

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

how does Ras work

A

when GDP phosphorylated to GTP and binds to Ras, it is active but once it binds to GDP, it becomes inactive so it needs constant stimulation to grow

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

how does Ras become constitutively active

A

when a mutation occurs that inhibits GTPase activity so Ras stays bound to GTP hence there is growth

mutation - single point mutants at Gly12 or Gln61

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what is usually seen with FISH probes in tumors where amplified region includes an oncogene

A

double minutes - extrachromosomal fragments of DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Abnormal Homogeneously Staining Regions of Chromosomes in Cancers Often contain

A

amplified oncogenes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

growth factor receptor

A

HER2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

cytosolic signal transducer

A

Ras

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

A clinical genomicist observes dmins (double minutes) in a metaphase spread. These aberrations result due to which of the following processes?

A

extrachromosomal fragments of DNA/ extrachromosomal gene amplifications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

A clinical genomicist observes hsrs (homogeneously staining regions) in a metaphase spread. These aberrations result due to which of the following processes

A

gene amplification in tandem

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

many inherited disposition to cancer result from mutations in

A

tumor suppressor genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

loss of function in the WT1 gene on chromosome 11

A

Wilms Tumor 11

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

what does the WT1 gene encode

A

transcription factor needed for cell growth and differentiation

41
Q

tumor suppressor gene encode for proteins that do what

A

stop cancer - DNA repair proteins, control cell cycle, promote apoptosis

42
Q

how many copies of the tumor suppress gene do you need to be mutated to have cancer

A

both copies need to be mutated - two hit hypothesis

43
Q

basis for the two hit hypothesis

A

familial and non familial (sporadic) forms of cancer exist

44
Q

-mutation occurs in tumor suppressor gene on one homolog in 1st hit/ 1st mutation one cell
-The second mutation occurs in the same gene (2nd copy) in the same cell
=loss of all tumor suppressor activity
= cancer



A

two hit hypothesis

45
Q

difference between familial and non familial forms of cancer

A

in familial, the first hit/mutation is inherited so it is present in all cells so only one more hit needed for mutation

while in nonfamilial, it is not inherited and two hits are needed in order to have a mutation

46
Q

second hit is usually what type of mutation

A

loss of heterozygosity

47
Q

how does loss of heterozygosity work

A

if a child is heterozygote at a locus but the tumor tissue has only a single type of allele, mutation would occur where child loses one of its alleles hence losing its heterozygote status

48
Q

4 mechanisms of 2nd hit that causes persons to lose its normal allele and retain its tumor allele (loss of heterozygosity)

A

loss through nondisjunction, mitotic recombination, gene deletion, and point mutation

49
Q

loss of tumor suppressor gene function is a result of

A

methylation of gene resulting in its silencing - so mutation in DNA silencing can result in tumor

50
Q

what does cyclin/Cdk do

A

it hyperphosphorylates Rb so that it no longer represses/binds to ECF so that it can activate S phase genes causing cells to divide

occurs in G1/S phase

51
Q

what happens if no cyclin/Cdk present

A

Rb is hypophosphorylated and it continues to bind/repress ECF then it recruits histone deacetylase and histone methylase so it cannot activate the S phase hence hindering transcription –> G1 cell cycle arrrest

52
Q

what happens if there is a mutation in Rb

A

cell cycle would not arrest at G1 even if Rb is hypophosphorylated and bound to histone methylase and histone deacetylase, ECF will still bind and cell division will progress —> uncontrolled cell division

53
Q

all cancer cells show dysregulation of the G1-S checkpoint as a result of mutations in what 4 genes that regulate the phosphorylation of Rb

A

Rb, CDK4, cyclin D gene, and CDKN2A (p16)

54
Q

mutation of Rb gene on chromosome 13

A

retinoblastoma (childhood cancer)

remember two copies of Rb gene have to be mutated to have the cancer

55
Q

in terms of familial cancers, what is inherited

A

the first hit is inherited through germline mutation

second hit is through somatic mutation

56
Q

in non familial cancer/ sporadic cancers, how many mutations are required for manifestations of cancer

A

two somatic mutation since none is inherited

57
Q

differences in familial and sporadic cancer

A

familial - appears autosomal dominant, multiple tumors, bilateral, early onset

sporadic - appears autosomal recessive, simple tumor, unilateral, late onset

58
Q

despite high penetrance why is it that some people who have germline mutation of cancer do not have cancer?

A

because the second hit/somatic mutation has not occurred yet

59
Q

so loss of Rb destroys what checkpoint

A

G1/S checkpoint

60
Q

loss of Rb or mutant Rb does what ?

A

does not bind to ECF hence does not suppress it leading to increased transcriptions of S phase genes leading to unregulated cell division

61
Q

tumor suppressor that controls both cell birth and cell death

A

p53

62
Q

what is p53

A

transcription factor activated by cell stress particularly DNA damage and it impinges on the G1/S checkpoint

63
Q

what happens with loss of p53

A

increased net cell growth and increased frequency in mutation (since no apoptosis)

64
Q

what exactly does p53 do

A

arrests cell cycle in G1, activates DNA repair if damage, if DNA damage is beyond repair it activates apoptosis

65
Q

guardian of the genome

A

p53

66
Q

p53 drives the expression of what apoptotic genes

A

pro-apoptotic Bcl-2 family members, Fas receptors (CD95), IGFBP-3 (sequesters cell survival proteins like IGF1/2 away from receptors)

67
Q

inherited mutation in p53 and some tp53 genes

A

Li Fraumeni Syndrome

68
Q

first hit in Li Fraumeni is from

A

mother

69
Q

Li Fraumeni can lead to

A

different types of cancers - breast, bone, brain, adrenocortical tumors and soft-tissue carcinomas

70
Q

p53 is regarded as the guardian of the genome
because, in response to DNA damage, this
transcription factor

A
  1. Activates the G1/S checkpoint
  2. Drives expression of DNA repair genes
  3. Promotes cell cycle arrest
  4. Initiates apoptosis of badly damaged cells
71
Q

common inherited cancers

A

colorectal:
familial adenomatous polyposis (FAP)
hereditary non-polyposis colon cancer (HPNCC): lynch syndrome

breast cancer

72
Q

mutation in the APC (adenomatous polypsis coli) gene on chromosome 5

A

FAP 5

73
Q

what does it mean if person has multiple polyps on colon

A

it means they have a higher chance of getting cancer and not that they have it - need second mutation to have the disease

it is best to get colon removed

74
Q

FAP has different mutations on the APC gene meaning that

A

it has allelic heterogenity

75
Q

in FAP, the tumor suppressor gene affects _____ involved in the control pathway

A

b-catenin

76
Q

normal APC pathway when there is no WNT signal

A

APC (part of WNT signaling pathway) degrades b-catenin by phosphorylation (ubiquitination) so with low beta catenin level there is no growth

77
Q

normal APC pathway when there is a WNT signal

A

destruction complex inactivated, beta catenin not degraded and enters the nucleus where it forms a complex with TCF-4 which activates growth promoting gene

78
Q

APC pathway when there is a mutation in APC

A

beta catenin is not phosphorylated and degraded by AFC in absence of WNT signal so it goes into nucleus and binds with TCF-4 where growth is activated

79
Q

which cells enter oncogene senescence

A

cells that gain oncogene signaling without loss of p53

80
Q

which one is an early gate keeper event and which on is late onset - APC and p53

A

p53 - late

APC - early

81
Q

mutation of DNA mismatch DNA repair genes (MMR)

A

HNPCC - hereditary non polyposis colon cancer: lynch syndrome

82
Q

difference between FAP and HPNCC

A

FAP has multiple polyps but progresses slowly

HNPCC has few polyps and progresses rapidly

83
Q

common genes responsible for HNPCC

A

MSH2 on chromosome 2
MLH1 on chromosome 1

locus heterogenity

84
Q

genes/proteins not directly involved in control of cell division

A

mutator genes

85
Q

lynch syndrome (tumor) exhibits what type of instability

A

microsatellite instability - short repetitive sequences of DNA

86
Q

A 28-year old male with family history of early colon cancer (prior to age 50) is examined by colonoscopy. A single large adenomatous polyp is discovered. Which of the following gene mutations is likely?

A

mutation in MSH2 or MLH1

87
Q

A 28-year old male with family history of early colon cancer (prior to age 50) is examined by colonoscopy. A single large adenomatous polyp is discovered. Which genomic aberration is most likely found in the tumor tissues

A

microsatellite instability

88
Q

breast and ovarian cancer exhibit what phenomenon

A

locus heterogenity - BRCA1 and BRCA2 gene

also exhibit allelic heterogenity on BRCA1

89
Q

BRCA1 and BRCA2 are involved in _______ and ________ when DNA can’t be repaired

A

DNA repair and apoptosis

90
Q

what happens if loss of BRCA1 gene

A

cells can replicate with DNA damage —> cancer

91
Q

HER-2 (Human Epidermal growth factor Receptor 2) over-expression in sporadic breast cancer shows what on the probe

A

double minute chromosomes - extra chromosomal fragments of DNA

92
Q

binds to HER2 and prevents binding of EGF to HER2

A

Herceptin

93
Q

Herceptin is effective in what tumors

A

Her2+ tumors but not in Her2- tumors

94
Q

what does herceptin do

A

decreased tumor cell proliferation

95
Q

Possible Direct Roles of Epigenetics in Tumorigenesis

A

1) Silencing of tumor suppressor loci causing cell overgrowth
2) Loss of imprinting causing activation of growth associated genes (e.g. IGF2)
3) MicroRNAs

96
Q

what does miRNA do

A

it targets specific mRNA and silences it

97
Q

possible effects of cancer on miRNA

A

reduction of those that could have inhibited oncogene RNA

increase in those that have target suppressor RNA

ALL BAD

98
Q

Determining changes in the expression of large numbers of genes between two groups is possible with

A

microarray analysis

Genetics (19 decks)

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