Lecture 18 - Cancer Flashcards
Mutations can occur
in any cell
Germline
Somatic
Germline mutation
Inherited, passed to next gen
gametes (egg or sperm cells)
eg born errors of metabolism
Somatic mutation
in other cells (except gamete)
not passed on
result in cancer
what mutation can result in cancer?
somatic
How many cells make up human body?
37.2 trillion cells
Human cells
grow, divide, renew
what is Cancer?
collection of related diseases and can start anywhere in body.
Cancer cells
no longer respond to signals that control cellular growth and death.
Over time cells become increasingly resistant to controls that maintain normal tissue — and divide more rapidly.
Despite multiple abnormalities, What do cancer cells evade?
programmed cell death.
In the late stages of cancer, cells…
break through normal tissue boundaries and metastasize
(spread) to new sites in body.
what underlies the development of cancer?
Multiple mutations
Cancer is the result of an accumulation of
mutations.
Most associated with DNA replication.
why does the incidence of cancer greatly increases with age?
The more times a cell divides, more likely it to gain a mutation -
How many genes encode proteins that normally regulate cell growth and division?
Hundred
What can lead to cancer?
Mutations that alter genes that regulate cell growth and division in somatic cells.
Mutations may be
Spontaneous (occur by chance)
Exposure to mutagen (Carcinogen)
what are the 2 types of genes that can cause cancer when mutated?
Tumor suppressor genes
Onco-genes
Car analogy
Car is…
Brake is…
Accelerator is…
cell proliferation/growth
Tumor suppressor genes
Onco-genes
Brake pedal are Tumor suppressor genes
Encode proteins that normally prevent uncontrolled cell growth e.g
• proteins that inhibit cell division
• Prevent other mutations (DNA repair enzymes)
Lack of Tumor suppressor genes
stimulate cell growth
- i.e. recessive mutations promote cancer
Accelerator are Onco-genes
Encode proteins that promote cell growth (cell division)
Cancer mutations increase activity of these genes.
Dominant mutations promote cancer
Tumor suppressor genes
mutations that decrease gene activity cause cancer
Tumor suppressor genes
Signal for cell division results in…
E2F transcription factor
going to nucleus.
Cell division genes can be expressed.
Tumor suppressor genes
What cause activation of the
E2F transcription factor?
Loss of function mutation in RB gene.
AND
Loss of function mutation in p16 gene
Oncogenes
result from mutations that increase gene activity.
Proto-oncogene
a normal gene that when mutated can promote uncontrolled cell growth.
Oncogenes
What Increased cell growth?
Mutations that imcrrease transcription
Mutations that increase protein activity
Chromosomal changes (Gene duplications, Translocation)
Oncogenes
Region controlling amount transcription…
Mutations that increase transcription…
Alter control region
Normal growth stimulating protein in excess
Increase cell growth
Oncogenes
Protein coding region…
Mutations that increase
protein activity…
A protein that is always active or is not degraded.
Increase cell growth.
Chromosomal changes
Gene duplications
and
Translocation
New control region
Increase cell growth
Chronic Myeloid Leukemia example of how
oncogene and tumor suppressor mutations lead to cancer
Leukemia is a group of
blood cancers that
begin in bone marrow and result in high numbers of abnormal blood cells.
blasts or leukemia cells.
abnormal blood cells that are not fully developed.
Chronic Myeloid Leukemia are
Mutations that cause blood cells in bone marrow to keep dividing.
results high number of leukemia cells that are not fully developed.
BCR gene + ABL gene
Philadelphia Translocation chromosome BCR - ABL gene (Oncogene gene)
Protein always active
Normal ABL protein needs
a cellular signal to activate it to promote cell division.
And Tyrosine Kinase.
Does BCR-ABL oncogene protein need a signal to promote cell division?
No
Genetic Predisposition
inherited mutations
increase chance of cancer
Inherited (germline) mutation
a tumor suppressor gene
Cancer treatments
- Surgery
- Radiation therapy
- Chemotherapy
- Targeted therapy
Surgery
remove cancer cells
Radiation therapy
targeted radiation to kill cancer cells
Chemotherapy
uses drugs that target dividing cells as cancer cells grow and divide rapidly – but it also affects normal cells.
Mercaptopurine – DNA base inhibits with enzymes that make dATP and dGTP nucleotides.
Adenine DNA base
Targeted therapy
drugs that target changes in cancer cell that allow them grow and divided.
Gleevac inhibits kinase activity BCR - ABL
