Brainscape's Knowledge GenomeTM

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


See full index

Questions > 7.8 TSG methylation > Flashcards

7.8 TSG methylation Flashcards

1
Q

What type of DNA modification is involved in the repression of tumor suppressor genes?

A

Methylation of CpG sequences

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

Where is methylation found in mammalian cells?

A

Only when cytosines are 5’ to guanosines (in CpG sequences)

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

What happens when CpG methylation occurs near a gene promoter?

A

It causes repression of transcription

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

What is the result when methyl groups are removed from CpG sequences near promoters?

A

Transcription of the gene is de-repressed

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

How does methylation of CpG sequences contribute to cancer development?

A

It inactivates tumor suppressor genes

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

What protein complexes are involved in the methylation-induced repression of transcription?

A

Complexes with a methyl-CpG binding subunit and a histone deacetylase (HDAC)

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

What role does HDAC play in methylation-induced gene silencing?

A

It removes acetate groups from histones, leading to transcriptional repression

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

What is the relationship between histone modification and CpG methylation?

A

Histone modifications like H3K9Me3 can precede CpG methylation

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

How is CpG methylation heritably passed down during cell division?

A

It is maintained through cell generations, ensuring stable gene silencing

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

What happens to overall methylation levels in cancer cell genomes during tumor progression?

A

The overall level of methylation decreases (global hypomethylation)

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

What are CpG islands, and why are they significant in cancer cells?

A

Regions with a high density of CpGs that, when methylated, can silence gene promoters

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

What percentage of human genes have CpG islands near their promoters?

A

About 70% (~14,000 genes)

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

How does promoter methylation affect the transcription of tumor suppressor genes?

A

It silences their expression, contributing to tumor progression

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

Which type of mutation mechanism might methylation surpass in the inactivation of tumor suppressor genes?

A

Somatic mutation

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

What phenotype do tumors with extensive CpG island methylation exhibit?

A

CpG island methylator phenotype (CIMP)

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

What enzyme is overexpressed in cancers with the CpG island methylator phenotype?

A

DNA methyltransferase 3B (DNMT3B)

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

How does overexpression of DNMT3B in genetically engineered mice affect tumor development?

A

It accelerates tumor formation

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

Why is the promoter methylation of candidate tumor suppressor genes difficult to interpret?

A

It may reflect normal differentiation programs rather than cancer-specific silencing

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

What two mechanisms can lead to the loss of tumor suppressor gene function by promoter methylation?

A

Independent methylation of both gene copies or LOH combined with methylation

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

What percentage of normal bronchial epithelial cells from smokers exhibit p16INK4A methylation?

A

0.44

21
Q

How frequently do loss of heterozygosity (LOH) events occur compared to promoter methylation events in tumors?

A

LOH events occur more frequently than promoter methylation events

22
Q

What does the study of morphologically normal bronchial epithelial cells reveal about gene methylation in tumor development?

A

Methylation of growth-controlling genes occurs early, before visible histological changes

23
Q

How are “caretaker” genes affected by promoter methylation during tumor formation?

A

They are often silenced, compromising genome integrity

24
Q

What is an example of a tumor suppressor gene silenced by promoter methylation in sporadic breast and ovarian cancers?

A

BRCA1

25
Q

How prevalent is BRCA1 promoter methylation in sporadic breast and ovarian carcinomas?

A

~50% in breast and ~40% in ovarian carcinomas

26
Q

What figure illustrates the methylation state of promoters in various human tumors?

A

Figure 7.18

27
Q

What does Figure 7.18 show about tumor suppressor genes and caretaker genes?

A

They undergo hypermethylation in many human cancers

28
Q

What percentage of non-small-cell lung carcinomas have at least one methylated gene promoter?

A

0.37

29
Q

What happens when more than one promoter is methylated in a tumor cell?

A

It can further enhance tumor progression

30
Q

How does retinoic acid normally affect epithelial cells?

A

It induces cell cycle arrest and differentiation

31
Q

Why are breast cancer cells often unresponsive to retinoic acid treatment?

A

The RARβ2 gene, encoding a retinoic acid receptor, is often silenced by promoter methylation

32
Q

How does trichostatin A (TSA) affect breast cancer cells?

A

It reverses histone deacetylation and reactivates RARβ2 gene expression

33
Q

What therapy does the effect of trichostatin A suggest for breast cancer?

A

A combination of TSA and retinoic acid to restore growth inhibition

34
Q

How does promoter methylation attract histone deacetylase (HDAC)?

A

Methylated CpGs recruit HDAC, leading to chromatin remodeling that blocks transcription

35
Q

What is the impact of HDAC activity on chromatin structure?

A

It makes chromatin compact, preventing transcription

36
Q

What is the effect of global hypomethylation on cancer genomes?

A

It can lead to chromosomal instability

37
Q

What role does promoter methylation play in familial cancer syndromes like retinoblastoma?

A

It can silence tumor suppressor genes in sporadic cases without germline mutations

38
Q

How does hypermethylation differ between different tumor types?

A

The frequency and extent of promoter methylation vary dramatically

39
Q

What type of genes are silenced by methylation during tumor formation?

A

Tumor suppressor genes and caretaker genes

40
Q

What is the CpG island methylator phenotype (CIMP)?

A

A phenotype where many CpG islands in gene promoters are hypermethylated

41
Q

How many genes may be hypermethylated in CIMP tumors?

A

As many as 1000 genes

42
Q

What is a consequence of BRCA1 gene promoter methylation in cancer cells?

A

Increased risk of breast and ovarian carcinomas

43
Q

What is the significance of histologically normal tissues showing promoter methylation?

A

They may serve as precursors for malignant growths

44
Q

How does trichostatin A reverse the effects of CpG methylation?

A

It inhibits HDAC, reactivating gene expression

45
Q

What is one method for detecting global hypomethylation in tumor genomes?

A

Using techniques described in Supplementary Sidebar 7.4

46
Q

How does DNA methylation contribute to chromosomal instability in cancer cells?

A

By leading to the loss of methyl groups from non-functional repeated sequences

47
Q

How might methylation of “innocent bystander” genes contribute to cancer?

A

These genes may be silenced inadvertently during genome-wide methylation events

48
Q

How is retinoic acid resistance related to CpG methylation in cancer cells?

A

Methylation of retinoic acid receptor genes prevents cell cycle arrest in response to retinoic acid

49
Q

How does methylation of the RARβ2 gene affect breast carcinoma cells?

A

It prevents them from responding to retinoic acid treatment

Questions (7 decks)

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