Cancer Genetics

Question 0

Types of cancer

Answer 0

Sarcoma-mesenchymal tissue (bone, cartilage, muscle, fat)
Carcinoma-epitheloid tissue
Hematopoietic/lymphoid-leukemia and lymphoma

Question 1

Tumor

Answer 1

Start as single cell with a mutation which proliferates to form a group of similarly abnormal cells (clonal)
Solid or dispersed (leukemia)
Benign or malignant (metastasize) ->cancer

Question 2

Characteristics of cancer

Answer 2

Mutation or loss of genes involved in cell control including growth/division, proliferation, metabolism
Mutations may be inherited or acquired
Somatic mutation (multi step process) is usually required for disease expression
Environmental influences
Chromosome instability (CIN)

Question 3

Oncogene

Answer 3

Unregulated cell growth and proliferation
Dominant (require only one mutation)
Carried by viruses (HPV)
Mutation of proto-oncogene

Question 4

Proto oncogene

Answer 4

Housekeeping genes involved in cell proliferation and development like growth factors, cell surface receptors, intracellular signal transduction etc.
Gain of function mutation
Dominant
Acquired
Often expressed as leukemias and lymphomas

Question 5

Chronic myelogenous leukemia (CML)

Answer 5

First leukemia associated with a genetic marker
Translocation between two chromosomes fuses proto oncogene with another gene causing loss of proper regulatory controls and overproduction of tyrosine kinase (cell cycle regulation)

Question 6

Acute promyelocytic leukemia (APL)

Answer 6

Translocation splits prone recognition site so fusion signal can be detected using FISH, confirmed by karyotype analysis
Proto oncogene related

Question 7

Tumor suppressor

Answer 7

Genetic element whose lose or inactivation allows the cell to display an alternate phenotype leading to neoplasticism growth
Recessive (need two mutations)
1 mutation may be inherited
Often expressed as solid tumors
Gatekeepers: suppress tumors by regulating cell cycle or growth inhibition
Caretakers: repair DNA damage and maintain genomic integrity (indirect, accumulation of errors)

Question 8

Karyotype of a malignant tumor

Answer 8

Benign tumors can have many chromosome abnormalities and malignant tumors may have none

Question 9

Rb1

Answer 9

Retinoblastoma directly related to mutations of Rb1 (functions in regulation of cell cycle, G1 to S, gatekeeper mutation)
Tumor of the retinoblasts (immature retinal cells), disease doesn’t occur after 5 years old
Disease can be unilateral (sporadic) or bilateral (inherited)
Treat with laser surgery or enucleation (removal of eye)

Question 10

Knudson’s “two hit” hypothesis

Answer 10

Must be two mutations per cell
If single mutation inherited, the likelihood of a second mutation is high
Diseases appears to be dominant from pedigree but tumor suppressors are recessive
Sporadic mutations: both mutations need to occur at somatic level

Question 11

Somatic vs familial

Answer 11

Older age of onset vs younger onset

Question 12

Li fraumeni

Answer 12

Familial cancer syndrome
Inherited mutation of p53 (loss of checkpoint control of DNA damage)
Has no one target tissue, not specific to one disease
Many different cancers may occur

Question 13

Breast cancer

Answer 13

Familial or sporadic
Errors in homologous recombination or DNA repair defects
Multiple mutations in BRCA1 and BRCA2 for familial
Increased risk in males and Ashkenazi Jewish people

Question 14

Breakage syndromes

Answer 14

Recessive
Chromosome instability (unequal sister chromatid exchanges are not repaired)
Defective DNA repair mechanisms (caretaker, handled by different enzymes)
Accumulation of mutations
Fanconi anemia, ataxia telangiectasia, breast cancer, HNPCC, bladder cancer

Question 15

Hereditary nonpolyposis colon cancer (HNPCC)

Answer 15

Mutations in mismatch repair genes (defect usually excised along with adjacent bases, then filled in)
If error not detected, there will be 2 cell populations, one with the correct sequence and one with a mutation
Accumulation of errors

Question 16

Micro satellites

Answer 16

Small repeats present throughout genome
Highly polymorphic in population 
Can be used to detect DNA repair defects because they are very sensitive them and are subject to replication error due to slippage 
Defects can alter number of repeats 
Indirect test

Question 17

Chromosome instability

Answer 17

Key player in cancers

Breakage, recombination, chromosome rearrangement, gain or loss of whole chromosomes

Question 18

Karyotype evolution

Answer 18

Change over time in karyotype due to a acquisition of different mutations

Question 19

Loss of heterozygosity

Answer 19

Apparent homozygosity or hemizygosity in a tissue that should be heterozygote
Probably due to disease

Question 20

Hematologic transplantation

Answer 20

For Hematologic disorders
Collect bone marrow stem cells from patient (autologous) or matched donor (allogenic)
Use chemo to destroy bone marrow
Infuse unaffected cells into blood stream
Stem cells will migrate to bone marrow and reestablish hemapoiesis
Allogenic problems: immunosuppressive and graft vs host disease
FISH can tell if transplant successful