Cancer Bio EXAM- topic 1 and 2

How do you classify the type of cancer?

By the tissue affected

What does the grade of a tumour mean?

Differentiation, nuclear and cytoplasmic abnormalities, number of mitoses, extension of necrosis...

How do you define the stage of a cancer?

TNM classification and number

What is TNM classification

T: size of the tumor

N: putative regional lymph node invasion

M: distant metastases

What are the main steps towards formation of a cancer?

Initiation→Promotion→ Progression-→ Metastasis

What genes are often associated with hereditary cancers?

BRCA1, BRCA2

What are the first 6 hallmarks of cancer?

1\.Sustained proliferation signals

2\.Evasion of growth supressors

3\.Invasion and metastasis

4\.Replicative immortality

5\.Sustained angiogensis

6\.Resisting cell death

What are the 4 next generation hallmarks of cancer?

1\.Evasion of the immune system

2\.Tumour promoting inflammation

3\.Genome instability and mutation

4\.Deregulating cellular energetics

What is the effect of a mutation of BRCA1?

Affects the ability to repair dsDNA breaks and affects checkpoint controls during the cell cycle

What class of drugs targets the hallmark “ Sustained proliferation signals”

EGFR inhibitors

What class of drugs targets the hallmark “Evasion of growth supressors”

CDK inhibitors

What class of drugs targets the hallmark “Invasion and metastasis”

Inhibitors of HGF/cMet

What class of drugs targets the hallmark “Replicative immortality”

\

Telomerase inhibitors

What class of drugs targets the hallmark ”Sustained angiogensis”

Inhbitors of VEGF signalling

What class of drugs targets the hallmark “Resisting cell death”

Proapoptotic drugs

What class of drugs targets the hallmark “Evasion of the immune system”

PDL-1 and PD-1 inhibitors

What class of drugs targets the hallmark “Tumour promoting inflammation”

selective anti-inflammatory drugs

What class of drugs targets the hallmark “Genome instability and mutation”

PARP inhibitors

What class of drugs targets the hallmark”Deregulating cellular energetics”

Aerobic glycolysis inhibitors

What is Ras and what does a mutation in Ras lead to?

Ras is a proto-oncogene. A mutation in RAS makes it stay in the LOCKED conformation or GTP conformation, which means that it is continuously activated and does not require any signal for it to stimulate cell division.

Describe “READERS” in epigenetics

specialized domain containing proteins that identify and interpret the modifications from Writers

Describe “WRITERS” in epigenetics

introduce various chemical modifications on DNA and histones

Describe “ERASERS” in epigenetics

proteins that are capable of removing modifications to DNA or histones that were produced by epigenetic writers to regulate gene expression

Epigenetic transcriptional control can occur through:

1\.DNA methylation

2\.Histone modification and chromatin remodelling

3\.Non-coding RNA's

Name 3 epigenetic writers

1. DNMTs
2. HMTs
3. HATs

Name one epigenetic reader

UHRF1

Name 3 epigenetic erasers

1\.DNA-demethylating enzymes

2\.KDMs

3\.HDACs

What do DNMTs catalyze

The addition of a methyl group to the 5th carbon position of cytosines, especially at a C followed by a guanine

What is the reaction of DNMT

cytosine→5-methylcytosine

What does DNA **hyper**methylation lead to?

Promoter silencing of tumorsuppressor genes

What does DNA **Hypo**methylation lead to?

Genome instability and Oncogene activation

What does high expression of UHRF1 lead to?

Hypermethylation→Inhibition of TSG

What kind of biomarker can UHRF1 be?

prognosis and diagnostic biomarker

What does UHRF1 bind to?

HDAC1 and DNMT1 through the SRA domain

What are the Ten-Eleven Translocation (TET) enzymes?

DNA-demethylating enzymes (Erasers)

What type of reactions do the TET enzymes do?

Oxidation reactions

What are the reaction steps catalyzed by the TET enzymes?

5-methylcytosine→5hydroxymethylcytosine →5-formylcytosine→5-carboxylcytosine

Are levels of 5-hydroxy-methylcytosine HIGH or LOW in cancer?

LOW

On which 2 amino acids does histone modification often occur?

Lysine and arginine

which domain of the histone is often methylated?

H3 tail

Is MLL a histone methylation reader, writer or eraser?

writer

What does MLL methylate?

H3K4

Low levels of histone modification is associated with good or bad survival prognosis in patients?

Bad prognosis

Name 2 histone methylation Readers:

HP1 and Chd1

Name a class of histone methylation erasers and two examples from this class:

HDMs (LSD and JMJC)

True or false “ Histone methylation can either promote or inhibit gene expression”

True

Name the class of histone acetylation writers:

KATs or HATs

Name the class of histone acetylation readers:

The BETs

What does BET stand for?

Bromodomain and extraterminal domain proteins

What is BET?

A histone acetylation reader

Name the 4 members of the BET family:

BRD2, BRD3, BRD4, BRDt

What is the name of the histone acetylation erasers?

HDACs

What happens when HDACs are disregulated?

Over de-acetylation and and inactivation of tumour supressor genes

True or False “ miRNA can be tumour-promoting and tumour-supressing”

True

What type of biomarker can miRNA be?

Predictive biomarkers