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FPP MSS > Molecular Oncogenesis > Flashcards

Molecular Oncogenesis Flashcards

1
Q

What drug is used to treat ERB B2 (Her-2-Neu) amplification? Seen in which type of cancer?

A

Trastuzumab (Herceptin) for ERB B2 amplification in breast cancer

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2
Q

What drug is used to treat c-KIT mutation in GISTs? What is it’s mechanism?

A

Imatinib (Gleevec) is a tyrosine kinase inhibitor

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3
Q

What is the single most common abnormality of oncogenes in tumors?

A

RAS oncogene point mutation

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4
Q

What is the SIS gene product B-PDGF and how does it lead to cancer?

A

It is a growth factor and when it is over expressed it causes astrocytoma and osteosarcomas.

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5
Q

How is the ERB B2 gene related to cancer? Which type?

A

It makes the HER2/Neu growth factor receptor. It is amplified in breast cancer.

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6
Q

How does amplification of the Her2/Neu receptor affect the prognosis of breast cancer?

A

It is a poor prognostic sign because it predicts unresponsiveness to estrogen therapy.

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7
Q

C-kit mutation is characteristic of which cancer? What is C-kit?

A

C-kit is a growth factor receptor that is mutated in gastrointestinal stromal tumors (GIST).

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8
Q

What are two examples of signal transducing proteins that are proto-oncogenes?

A

Ras oncogene family and c-ABL gene

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9
Q

What is the c-ABL gene? What kind of cancer does it cause?

A

c-ABL makes a signal transducing protein with transient tyrosine kinase activity. When there is a translocation (9,22) a bcr-abl fusion product is created. This causes Chronic Myelogenous Leukemia because there is loss of regulatory control.

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10
Q

What is the translocation that causes Chronic Myelogenous Leukemia?

A

Translocation (9,22) that produces bcr-abl fusion product. Philadelphia chromosome.

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11
Q

What does c-MYC encode? It is expressed in what cancer?

A

It encodes a transcription factor. Translocation (8,14) of the myc gene to the immunoglobulin heavy chain gene on chromosome 14 causes over expression. This leads to Burkitt’s lymphoma.

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12
Q

How does n-MYC cause cancer?

A

Amplification of n-myc is seen in neuroblastoma. This is associated with poor prognosis of neuroblastoma.

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13
Q

What cell cycle regulators can become oncogenes?

A

Cyclin D1 can be translocated from 11 to the IgH gene of chromosome 14. This causes over expression and results in mantle cell lymphoma.

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14
Q

What is cyclin D?

A

It activates CDK4 and the complex phosphorylates Rb to inactivate it and stimulate cell cycle.

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15
Q

What is the Rb gene?

A

A tumor suppressor gene that is a cell cycle regulator.

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16
Q

How does Rb lead to cancer?

A

Mutations of Rb cause failure of E2F regulation allowing for unregulated cell growth. This causes retinoblastoma if both the Rb alleles are mutated.

17
Q

What is APC?

A

A tumor suppressor gene that is involved in destruction of B-catenin.

18
Q

What is B-catenin?

A

It regulates nucleic acid expression in the nucleus. When APC is mutated, B-catenin accumulates and complexes with TF leading to unregulated cell growth and adenomas.

19
Q

What cancer is unregulated B-catenin associated with?

A

Familial adenomatous polyposis.

20
Q

What is the treatment for familial adenomatous polyposis?

A

Prophylactic colectomy

21
Q

What is the cause of Li-Fraumeni Syndrome?

A

Inherited mutation of p53 tumor suppressor allele.

22
Q

What does Li-Fraumeni Syndrome cause?

A

25x risk of developing cancer by 50y/o (sarcoma, carcinoma, leukemia)

23
Q

What is Bcl-2?

A

Anti-apoptotic gene that prevents cells from undergoing apoptosis

24
Q

How does Bcl-2 lead to cancer? Which type?

A

Translocation (14;18) causes IgH bcl-2 fusion. The bcl-2 gene goes from chromosome 18 to 14 and causes inhibition of normal apoptosis. This causes slow growing follicular lymphoma.

25
Q

What is CYPIAI?

A

It is a p450 enzyme that metabolizes polycyclic aromatic hydrocarbons. 10% of caucasians have inducible form that leads to increased carcinogens and risk of cancer.

26
Q

What is glutathione-S-transferase?

A

It is an enzyme that detoxifies polycyclic aromatic hydrocarbons. 50% of caucasians have deletions that lead to increased risk of carcinogens and risk of cancer.

27
Q

What is an initiator?

A

A chemical that causes permanent DNA mutations. Direct or indirect acting compounds.

28
Q

What is a promoter? Name 2 examples.

A

A non-tumorigenic chemical that enhances the proliferation of mutated cells. Effort is reversible. Hormones, phenols, alcohol, bile salts.

FPP MSS (6 decks)

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