Transcript Understanding SNPs and Cancer

3.1.3.A
Understanding Cancer
What is Cancer
What Is Cancer?
Different Kinds of Cancer
Some common
carcinomas:
Lung
Leukemias:
Bloodstream
Lymphomas:
Lymph nodes
Breast (women)
Colon
Bladder
Prostate (men)
Some common
sarcomas:
Fat
Bone
Muscle
Cancer is Complex
Naming Cancers
Cancer Prefixes Point to Location
Prefix
Meaning
adeno-
gland
chondro-
cartilage
erythro-
red blood cell
hemangio- blood vessels
hepato-
liver
lipo-
fat
lympho-
lymphocyte
melano-
pigment cell
myelo-
bone marrow
myo-
muscle
osteo-
bone
Loss of Normal Growth Control
Normal
cell division
Cell Suicide or Apoptosis
Cell damage—
no repair
Cancer
cell division
First
mutation
Second
mutation
Third
Fourth or
mutation later mutation
Uncontrolled growth
Example of Normal Growth
Dead cells
shed from
outer surface
Epidermis
Dividing cells
in basal layer
Cell migration
Cell Division
Dermis
Balance between cell death and cell production
The Beginning of Cancerous Growth
basal cells now divide faster
than is needed to replenish
the cells being shed from the
surface of the skin.
Both daughter cells retain
capacity to divide.
Underlying tissue
Tumors (Neoplasms)
Neoplasm (new formation/creation)
Increased rate of cell division
Decreased (or no) apoptosis to
compensate
Underlying tissue
Invasion and Metastasis
Cancers spread using 2 mechanisms:
• invasion
• metastasis
1
Cancer cells invade
surrounding tissues
and blood vessels
2
Cancer cells are
transported by the
circulatory system
to distant sites
3
Cancer cells
reinvade and grow
at new location
Invasion and Metastasis
Invasion - direct migration and penetration by cancer
cells into neighboring tissues.
Metastasis - ability of cancer cells to penetrate into
lymphatic and blood vessels, circulate through the
bloodstream, and then invade normal tissues
elsewhere in the body.
VIDEO
Malignant versus Benign Tumors
Benign (not cancer)
tumor cells grow
only locally and cannot
spread by invasion or
metastasis
Time
Malignant (cancer)
cells invade
neighboring tissues,
enter blood vessels,
and metastasize to
different sites
By definition the term “cancer”
applies only to malignant tumors
Why Cancer Is Potentially Dangerous
Brain
2
Cancer cells in the liver
would be called metastatic
melanoma, not liver
cancer.
3
1
Liver
Melanoma
(initial tumor)
Melanoma
cells travel
through
bloodstream
Genes and Cancer
Viruses
Chemicals
Radiation
Heredity
Chromosomes
are DNA
molecules
DNA Structure
Chemical
bases
A
C
DNA molecule
T
G
DNA Mutation
DNA
CA AG C T A A C T
Normal gene
CA AG C G A A C T
Single base change
CA A G G CG C T A A C T
Additions
C
T
CA A G A A C T
Deletions
Oncogenes
Normal cell
Cancer cell
Mutated/damaged oncogene
Normal
genes
regulate
cell growth
Oncogenes
accelerate
cell growth
and division
Oncogenes
An oncogene is a gene that has the potential to cause cancer.
Categories:
Growth factors - Induces cell proliferation
Receptor tyrosine kinases – Cell signaling
Cytoplasmic tyrosine kinases – Cell signaling
Cytoplasmic Serine/threonine kinases – Cell signaling
Regulatory GTPases – Cell signaling
Transcription factors – Regulates gene transcription
In tumor cells oncogenes are often mutated or
expressed at high levels.
Oncogenes
Most normal cells undergo apoptosis
Activated oncogenes can cause those cells designated for
apoptosis to survive and proliferate instead
Most oncogenes require an additional step, such as
mutations in another gene, or environmental factors, such as
viral infection, to cause cancer
1970 – First oncogene identified (dozens identified since)
Many cancer drugs target proteins encoded by oncogenes.
Proto-Oncogenes and Normal Cell Growth
A proto-oncogene is a normal gene that can become an oncogene
due to mutations or increased expression
Growth factor
Receptor
Signaling enzymes
Transcription
factors
Cell nucleus
DNA
Cell proliferation
Normal Growth-Control Pathway
Oncogenes are
Mutant Forms of Proto-Oncogenes
Inactive growth factor receptor
Inactive intracellular
signaling protein
Signaling protein from active oncogene
Activated gene
regulatory protein
Transcription
Cell proliferation driven by
internal oncogene signaling
Tumor Suppressor Genes
Normal
genes
prevent
cancer
Normal cell
Remove or inactivate
tumor suppressor genes
Cancer cell
Damage to
both genes
leads to
cancer
Mutated/inactivated
tumor suppressor genes
Tumor Suppressor Genes
Individuals who inherit an increased risk of developing
cancer often are born with one defective copy of a
tumor suppressor gene.
Because genes come in pairs (one inherited from each
parent), an inherited defect in one copy will not lead to
cancer because the other normal copy is still
functional.
But if the second copy undergoes mutation, the person
then may develop cancer because there no longer is
any functional copy of the gene.
Tumor Suppressor Genes
Act Like a Brake Pedal
Tumor Suppressor
Gene Proteins
Growth factor
Restrains cell
growth and
division
Receptor
Signaling
enzymes
Cell nucleus
Transcription
factors
DNA
Cell proliferation
p53 Tumor Suppressor Protein
Triggers Cell Suicide
p53 protein
Normal cell
Excessive DNA damage
(repair not possible)
Cell suicide
(Apoptosis)
DNA Repair Genes
Normal DNA repair
T C GA C
Base pair
mismatch
No cancer
TC T AC
AG C T G
TC TAC
TCT AC
AG C T G
Cancer
AG
TG
AG A T G
No DNA repair
DNA Repair Genes
Xeroderma pigmentosum
• Inherited defect in a DNA repair gene.
• Patients cannot effectively repair the
DNA damage that normally occurs
when skin cells are exposed to
sunlight
• Exhibit an abnormally high incidence
of skin cancer
Certain forms of hereditary colon cancer also
involve defects in DNA repair.
Cancer Tends to Involve Multiple Mutations
Benign tumor cells
grow only locally and
cannot spread by
invasion or metastasis
Malignant cells invade
neighboring tissues, enter
blood vessels, and
metastasize to different sites
Time
Mutation
Cells
inactivates proliferate
suppressor
gene
Mutations
inactivate
DNA repair
genes
Proto-oncogenes
mutate to
oncogenes
More mutations,
more genetic
instability,
metastatic
disease
Mutations and Cancer
Genes Implicated in Cancer
Cancer Tends to
Corrupt Surrounding Environment
Growth factors = proliferation
Invasive
Matrix
Proteases
Fibroblasts,
adipocytes
Blood vessel
Cytokines, proteases = migration & invasion
Cytokines