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BB20149 > Epigenetics and cancer > Flashcards

Epigenetics and cancer Flashcards

1
Q

What percentage of CpGs are methylated?

A

60-80%.

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2
Q

What is CpG?

A

Regions of DNA where a cytosine is followed by a guanine nucleotide in the sequence.

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3
Q

What percentage of CpGs are present in CpG islands?

A

10%.

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4
Q

What is a CpG island?

A

THey are 100kb - 2kb dense CpGs.

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5
Q

Where are CGIs usually found, and is the DNA methylated or unmethylated??

A

At promoters and unmethylated.

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6
Q

When is DNA remethylated in sperm?

A

Before birth and after meiosis.

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7
Q

What is a consequence if methylation is defective?

A

Spermatogenesis is impaired.

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8
Q

When is DNA fully remethylated in eggs?

A

After meiosis 1 arrest and sexual maturation.

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9
Q

What is the result of defective methylation in oocytes?

A

It does NOT hinder fertilisation.

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10
Q

When does DNA methylation decrease in male DNA?

A

Just after fertilisation to up until morula stage. It decreases rapidly in comparison to female DNA.

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11
Q

When does DNA methylation decrease in female DNA?

A

From past the zygote stage and slowly decreases until the morula stage.

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12
Q

What are some ways in which DNA can be demethylated?

A

TETs - oxidative demethylation and ELP3.

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13
Q

What is another method in which DNA can be demethylated?

A

The DNA can be deaminated followed by repairing the T-G mismatch.

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14
Q

What are the Tet genes?

A

Tet1, Tet2 and Tet3.

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15
Q

How does the expression of Tet change throughout development?

A

Tet3 has high expression at the zygote stage and decreases until the two cell stage where it is no longer present, whereas Tet1 and Tet2 are not present until just after the four cell stage and increase until up to the blastocyst stage.

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16
Q

What is 5-mC?

A

Methylayed DNA.

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17
Q

What is 5-hmC?

A

Hydroxymethyl group on DNA - involved in switching genes on and off.

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18
Q

What does De novo methylation of Oct5 and Nanog result in?

A

The silencing of Nanog and Oct4.

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19
Q

What demethylates Oct4 and Nanog?

A

DNMT3A and 3B.

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20
Q

What can be derived from embryonic stem cells in the lab?

A

Germline, endoderm, mesoderm and ectoderm.

21
Q

What use does the development of germline cells have in the lab?

A

Can be used to treat infertility.

22
Q

What use does the development of endoderm cells have in the lab?

A

Can be used to treat disease of the lung, gut or liver such as COPD, diabetes and cirrhosis.

23
Q

What use does the development of mesoderm cells have in the lab?

A

Can be used to treat disease of the muscle, blood, bone and cartilage such as heart failure, anemia, leukemia, arthritis and bone fracture.

24
Q

What use does the development of ectoderm cells have in the lab?

A

Can be used to treat disease of the brain and skin such as macular degeneration, Parkinson’s disease and ALS.

25
Q

How can iPSCs be generated?

A

Replacing Oct4 with Tet1, as Tet1 facilitates iPSC induction by promoting Oct4 demethylation and reactivation.

26
Q

What can human primordial germ cell migration lead to?

A

Ectopic localisation - sacro-coccgeal, retro-periotoneal, mediastinal, intracranial and epiphyseal regions ?????

27
Q

What are the most common childhood cancers, listed from most common to least common?

A

Leukaemia, brain tumours, lymphomas, neuroblastoma, Wilms, Rabdomyosarcoma.

28
Q

What do germ cell cancers arise from?

A

Primordial germ cells (despite presenting predominantly after puberty).

29
Q

What is the case with the PGCs in germ cell cancers?

A

The PGCs have failed to mature into pre-spermatogonia or oogonia.

30
Q

What do germ cell cancers mimic?

A

Embryonal development - they express OCT3/4, SOX2 and are overall demethylated.

31
Q

Why are germ cell cancers unusual?

A

They are no/few genetic mutations, unlike most solid tumours.

32
Q

What percentage of tumours in children-adolescents originate from PGCs?

A

4%.

33
Q

When do tumours that arise from germ cells usually emerge?

A

During puberty, but can occur before age 3.

34
Q

What percentage of germ cell tumours are benign?

A

66%.

35
Q

What are Germinoma?

A

A type of germ cell tumour that is not differentiated upon examination. It may be benign or malignant.

36
Q

What is seminoma?

A

A germ cell tumour in the testes.

37
Q

What is a dysgerminoma?

A

A type of germ cell tumour usually in the ovaries. It is usually malignant.

38
Q

What are the classifications of germ cell tumours?

A

Germ cell stage (germinoma, seminoma, dysgerminoma), embryonic tumours and extraembryonic tumours.

39
Q

When are germinonas most commonly diagnosed?

A

Second and third decades of life.

40
Q

What is the gender predominance with germinoma?

A

Strong male predominance.

41
Q

Where are germinoma most commonly found?

A

In the brain - PGCs migrate incorrectly.

42
Q

What is a teratoma?

A

A tumour with tissue or organ components, resembling normal derivatives of more than one germ layer.

43
Q

What is a gonadoblastoma?

A

A complex tumour composed of a mixture of large primordial germ cells, immature sertoli cells or granulosa cells of the sex cord and gonadal stromal cells.

44
Q

What is Tatten-Brown-Rahman syndrome (TBRS)?

A

It is an overgrowth syndrome - growth rate is increased before and after birth. It includes heart defects, curvature of the upper spine, flat feet, weak muscle tone and loose flexible joints. May also show autism and learning difficulties.

45
Q

What is TBRS caused by?

A

A mutation in DNMT3A.

46
Q

What is Sotos syndrome?

A

An overgrowth syndrome.

47
Q

What is the cause of Sotos syndrome?

A

Haploinsufficiency of NSD1, a histone methyltransferase that catalyses the dimethylation of histone H3 at K36 (H3K36me2).

48
Q

What are the similarities between Sotos and TBRS?

A

They are both overgrowth conditions and are both susceptible to Wilms tumour, neuroblastoma, sacroccygeal teratoma and acute myeloid leukaemia.

BB20149 (16 decks)

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