Cancer Genetics and Genomics

Question 1

Clonal disorder

Answer 1

All cells in a tumor arise from a single cell whose growth control has gone wrong

Question 2

Properties of Malignant Cells

Answer 2

Immortal
Grow more rapidly than normal cells of the same origin
Fail to exhibit normal cell-cell interactions

Question 3

Multi-hit hypothesis

Answer 3

Numerous genetic abnormalities must accumulate to promote the evolution of a tumor

Question 4

Proto-oncogenes

Answer 4

Genes that encode proteins that are integral for the normal growth of the cell, particularly those involved in cell-cell interactions, cell cycle, and signal transduction

Question 5

Oncogenes

Answer 5

Genes that have undergone mutations such that the proteins they encode no longer function appropriately in the cell –> unregulated cell growth and proliferation

Question 6

Gleevec

Answer 6

Used for treatment of chronic myelogenous leukemia b/c of its ability to selectively inactivate the ber-abl fusion kinase but not the normal abl kinase

Question 7

Result of a gain-in-function mutation?

Answer 7

B/c gain-of-function mutations that interfere with proper regulation of proto-oncogenic activities or that amplify the # of copies of proto oncogenes can lead to disregulation of the oncogenic activity

Question 8

Why do oncogenes act in a dominant fashion at the cellular level?

Answer 8

Only one of the 2 genes homologs needs to be defective in order for the protein to cause problems in the physiology of the cell

Question 9

Proteins encoded by oncogenes?

Answer 9

growth factors, growth factor receptors, signal transduction molecules, nuclear transcription (same as proto-oncogenes)

Question 10

Onco-miRs

Answer 10

miRNA molecules that are responsible for the post-transcriptional regulation of upwards of 200 unique genetic targets per miRNA gene

Some the miRNAs act as oncogenes and inhibit large numbers of tumor suppressor genes

Question 11

Tumor suppressor genes

Answer 11

Genes that encode proteins whose normal physiological role is largely to prevent the rampant proliferation of cells

are loss-of-function mutations that act in a recessive fashion at the cellular level
*both copies of the tumor suppressor gene must be inactivated in order for tumorigenesis to occur

Question 12

Caretaker genes

Answer 12

Tumor suppressors

DNA repair genes

Question 13

Gatekeeper genes

Answer 13

Tumor suppressors

Cell cycle checkpoint genes

Question 14

Xeroderma Pigmentosum

Answer 14

Mutation in genes required for nucleotide excision repair
Sensitive to UV radiation

recessive chromosome instability syndrome

Question 15

Ataxia Telangiectasia

Answer 15

ATM mutation prevents proper DNA damage repair for double stranded breaks

Presence of DNA free ends generates a highly unstable genomic state and these fusogenic ends often associate to create new translocations

Karyotype: long chromosome with many constriction points
recessive chromosome instability syndrome

Question 16

Fanconi Anemia

Answer 16

Patients harbor genetic lesions in proteins that interact with ATM
Also acutely sensitive to agents that cause double-stranded breaks

Symptoms: bone marrow failure

recessive chromosome instability syndrome

Question 17

Bloom Syndrome

Answer 17

Mutations in another protein complex that interacts with ATM and Fanconi patients

Symptoms: repeated otitis media and pneumonia, early menopause, a wide variety of cancer susceptibilities

recessive chromosome instability syndrome

Question 18

RB1- 2 hit hypothesis

Answer 18

Both copies of RB1 must be inactivated to promote tumor development

*incomplete penetrance b/c some people with the predisposition of rb do not end up getting the tumor even though high chance that it you have 1 mutated copy, the other will also be mutated

Question 19

Tumor suppressor- familial inheritance

Answer 19

Inherited in apparent dominant fashion

Question 20

Loss of heterozygosity

Answer 20

Acquiring a hereditary mutation in a tumor suppressor predisposes an individual to these effects

Heterozygous individuals have a higher likelihood of acquiring a mutation (ie: deletion) in the single remaining wild type allele of the gene

ie: p53- Li Fraumeni syndrome