4 Flashcards

(17 cards)

1
Q

What is ‘haploinsufficiency’?

A

The idea that it only takes one hit to give the cell a selective advantage – a 50% decrease in protein is sufficient to give the cell a selective advantage

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2
Q

Describe, broadly speaking, how translocations can cause cancer.

A

The translocation could lead to the formation of a new fusion gene that encodes a protein that has oncogenic properties

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3
Q

What protein does the fusion gene in Chronic Myelocytic Leukaemia produce?

A

BCR-ABL1 Tyrosine Kinase

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4
Q

What are two diseases that predispose to colorectal cancer and what are the relative risks?

A

Familial Adenomatous Polyposis – nearly 100%

Hereditary Non-Polyposis Colorectal Cancer (Lynch Syndrome) –80%

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5
Q

Describe, using an example, a targeted therapy for CML.

A

Imatinib – inhibits the BCR-ABL1 tyrosine kinase

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6
Q

What are ‘cytogenic changes’?

A

Visible changes in chromosome structure or number

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7
Q

What is the point in pharmacogenomics?

A

Using genetics to determine which patients will respond best to particular treatments

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8
Q

What are the normal functions of tumour suppressor genes?

A

Regulate cell division Regulates apoptosis Regulates DNA Repair
Monitors DNA damage checkpoint TSG is recessive

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9
Q

What treatment is available for acute promyelocytic leukemia and how does it work?

A

All Trans Retinoic Acid (ATRA)

Binds to the DNA with greater affinity than the mutated RARA thus preventing gene silencing

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10
Q

Describe the two hit hypothesis.

A

It takes two hits (both TSG must be mutated) for a cancer to start The first hit is usually a mutation The second hit is usually a larger deletion that removes the other allele and hence the function of the gene completely

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11
Q

What is a common manifestation of the second hit?

A

Loss of heterozygosity – the deletion could remove other genes that are part of a heterozygous pair
This means that that gene then appears homozygous as one of the alleles has been los

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12
Q

What genes predispose to breast and ovarian cancer and what is the lifetime risk?

A

BRCA1 and BRCA2
60% in women
? in men

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13
Q

Explain the cause of Chronic Myeloid Leukaemia.

A

Translocation between chromosome 9 and 22
BCR gene from chromosome 22 and ABL gene from chromosome 9 fuse in the newly formed Philadelphia chromosome.
The BCR-ABL fusion gene encodes BCR-ABL1 tyrosine kinase, which promotes CML

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14
Q

What are the three techniques of quantifying the level of CML in order of sensitivity?

A

Cytogenetic analysis
Fluorescence in situ hybridisation
RT-qPCR (Reverse Transcriptase Quantitative PCR)

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15
Q

Describe the patho-genetic mechanism of BRCA genes.

A

BRCA genes are DNA repair genes (specifically, a process called homologous recombination)
When these DNA repair genes are mutated the DNA repair proteins are impaired leading to dysfunctional DNA repair proteins which causes many further mutations

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16
Q

Which two genes are involved in the translocation causing acute premyelocytic leukaemia?

A

Chromosome 15 = PML (Promyelocytic Leukaemia)

Chromosome 17 = RARA (Retinoic Acid Receptor Alpha)

17
Q

How does the PML/RARA translocation cause cancer?

A

RARA is a receptor that binds to Vitamin A and then binds to DNA and regulates transcription
The translocation and resulting gene fusion changes RARA so that it binds to DNA too strongly
These genes become silenced – the cell proliferates