Cancer Genetics 1 Flashcards

Question

What are the tumor suppressor genes?

Answer 1

- regulate cell-cycle checkpoints and/or initiate process of apoptosis - mutation in tumor suppressor genes result in uncontrolled cell division

Answer 2

- genes code for proteins involved in DNA repair | - Mutations in DNA repair genes increases the risk of cancer

Answer 3

Mutated or aberrantly expressed proto-oncogene is converted to an oncogene - has a gain of function alteration - Contributes to development of cancer and increases rate of cell division - Only one allele needs to be mutated or misexpressed to contribute to cancer - confers a dominant cancer phenotype

Answer 4

Regulate cell cycle checkpoints and initiate process of apoptosis

Answer 5

- cells are unable to respond to cell-cycle checkpoints or undergo apoptosis - this leads to more mutations and development of cancer - loss of function mutations - Both copies must be lost to result in cancer (recessive at the tumor level)

Answer 6

1. Growth factors (EGF) bind to receptors on cell surface 2. Growth factor-receptor complex activates intracellular proteins (ras) 3. Activation of ras results in activation of downstream proteins 4. Activation of nuclear transcription factors 5. Result in expression of proteins required for cell division /proliferation 6. Cell moves from G1(G0) phase to S phase (DNA synthesis /DNA replication)

Answer 7

- Code for proteins involved in growth factor signal transduction cascade(growth factor pathway ) - Proteins are normally synthesized in small amounts and well regulated

Answer 8

May result in: -Increased expression of the gene- resulting in increased levels of protein synthesis (greater stimulation for cell division) OR Altered protein that is not regulated and is constantly active (constitutively active)

Answer 9

A GTP binding cytosolic protein Ras-GTP is the active form - triggers downstream signals for cell division Ras is inactivated by hydrolysis of GTP to GDP; Ras-GDP is inactive

Answer 10

1. Growth factor binds to cell-surface receptor 2. Ras transiently exchanges GTP for GDP 3. Ras sends signals to cascades of activated proteins 4. Signal transduction proteins activate transcription factors 5. Activation or repression of gene expression

Answer 11

- overexpression of Ras- resulting in overproduction in constant activation of cell division - Mutant ras which is constantly active (point mutations ); Generally, mutant ras loses its GTPase activity and is constitutively active

Answer 12

- frequently mutated in cancer - encode signal transduction molecules associated with cell membrane - Regulate cell growth and division

Answer 13

- abl codes for tyrosine kinase in growth factor pathway | - abl protein is stringently regulated

Answer 14

- translocation of ABL gene on chromosome 9 to BCR gene on chromosome 22 - Philadelphia chromosome - abl gene is next to bcr to form a bcr-abl fusion gene - transcription and translation of the fusion gene results in synthesis of bcr-abl fusion protein - bcr-abl fusion protein has unregulated tyrosine kinase activity and is always active; it sends constant signals to the cell to keep dividing

Answer 15

Inhibition of bcr-abl fusion protein - Imantib mesylate (Gleevec) is an inhibitor of bcr-abl tyrosine kinase - Used in treatment of Ph+CML - Gleevec binds to and inhibits tyrosine kinase activity - As a result, downstream proteins are not phosphorylated and activated (cell division signal is inhibited)

Answer 16

Oncogene amplification May be seen in rapidly progressive cancer -presence of hundreds of copies of an oncogene in cancer cells - Oncogene amplification May be present as: - double minutes (extrachromosomal fragments of the oncogenes) - homogenously staining regions (multiple copies of the oncogene on a chromosome ) - Amplification results in synthesis of large quantities (overexpression) of oncoprotein and hence an increased stimulation for the cell to divide (uncontrolled cell division ) - Double minutes or horse indicate impaired DNA repair