Oncogenes- Lecture 54

Question 1

What are the mechanisms through which oncogenes act?

Answer 1

1. viral genome contains an activated form of a cellular gene/ the viral genome itself contains the oncogene (eg. RSV)
2. virus integrates in a genomic locus that results in aberrant expression of a cellular gene

Question 2

What are the mechanisms of activation for oncogenes in human cancer?

Answer 2

deletion/point mutation in coding sequence
regulating mutation
gene amplification
chromosome rearrangement

Question 3

_____ into the host genome and can lead to aberrant expression of a cellular gene involved in oncogenesis.

Answer 3

ALV inserts

Question 4

Missense mutations result in _____ of certain proteins.

Answer 4

constitutive activation

Question 5

What are the most common missense mutations that contribute to human cancers and what do they result in?

Answer 5

Ras (G12V or G13V) results in a oss of GTPase activity

Raf (V600E) leading to constitutive activation as a kinase is often found in melanoma

Question 6

What are the ways gene amplification results in oncogenesis?

Answer 6

gene limiting (eg. Myc, Cyclin D1, adn Ckd4)
growth factor receptors (eg. EGFR and Her2)
autocrine loop (eg. overexpression of PDGF)

Question 7

How can chromosomal translocations arise?

Answer 7

reciprocal translocation between two different chromosomes
inversion within the same chromosome
Either of these could involve regulatory regions (alter expression of a normal protein) or coding regions (resulting in expression of a novel, fusion protein)

Question 8

Provide examples of transcriptional regulation of relevant genes altered by gene rearrangements.

Answer 8

Burkitt’s Lymphoma (t(8;14))
Folicular B-cell lymphoma (t(14;18))
Inversion of chromosome 11

Question 9

Provide examples of how gene rearrangement involving coding regions results in transcriptional over-expression.

Answer 9

Chronic myelogenous leukemia (CML)- Philidelphia chromosome translocation of 9q+ 22q+
Acute Promyelogetic Leukemia (APL) t(15;17)

Question 10

What can you use to treat CML?

Answer 10

Gleevec- inhibits BcrAb1