Lectures 14 & 15: Cancer Genetics Flashcards
What is cancer the result of?
env + genetic makeup
Can a mutated cell in a tumor be traced back to the original mutant cell line? What is this called?
yes
tumors are clonal - single cell mutates, proliferates to form group of similarly abnormal cells
What is metastasis?
cells become invasive or move to another site
retain orignal morphology
still referred to by original site
In what tissues does sarcoma occur?
mesenchymal
bone, cartilage, muscle, fat
In what tissues does carcinoma occur?
epitheloid
In what tissues does hematopoietic/lymphoid cancer occur?
leukemia - in WBC from bone marrow
lymphoma - WBC from spleen and lymph nodes
What are some environmental mutagens?
UV light, asbestos, cig smoke, plastics, dyes
Red dye #3 banned
What is chromosome instability? What is it a hallmark of?
gain, loss, or rearrangement of xs
cancer
What types of genes are associated with cancer?
Tumor suppressors
Oncogenes/proto-oncogenes
Where do oncogenes in humans come from?
Viruses
mutations of proto-oncogenes
What are examples of viral oncogenes in humans?
HPV EBV HIV-8 HTLV-1 (leukemia) HTLV-2 (leukemia)
How are oncogenes defined? What are the involved in?
Dominant acting gene
involved in unregulated cel growth and proliferation
What are examples of viral oncogenes in animals?
H-ras
sis
abl - Abelson murine leukemia virus
What is the normal function of proto-oncogenes in humans?
housekeeping - cell proliferation and development
What are examples of proto-oncogenes in humans?
GF Cell surface receptors intracellular signal transduction DNA BP (txn factors) Reg of cell cycle
How are proto-oncogenes “activated” (become cancerous)?
mutation (translocation, amplification, pt mutation)
Are proto-oncogene mutations dominant or recessive? How many gain of function mutations are needed?
dominant
one
What causes Chronic Myelogenous Leukemia?
activation of proto-oncogene
translocation between xs 22 and 9 forms Philadelphia xs
What is the Philadelphia chromosome, and what molecule does it affect?
translocation between proto-oncogene with second gene to form chimeric protein
overproduce tyrosine kinase (cell cycle reg)
What drug is used to treat CML? What is its target?
Gleevec
bcr/abl specific tyrosine kinase inhibitor
Why was Gleevec (treating CML) novel?
targets genetic lesion
How is Acute promyelicytic leukemia caused?
proto-oncogene activation
translocation –> chimeric protein product
PML gene on xs 15; RARA gene on xs 17
How is acute promyelicytic leukemia confirmed?
FISH immediately
confirmed by karyotype analysis
