Final: Cancer Genetics Flashcards
what is cancer
a genetic disease of cells in multicellular organisms
how does cancer begin
with genes that are supposed to regulate cell growth and division in organs of the body
complicated process
progression of cancer
starts with a single cell that acquires multiple mutations
each mutation along the way starts a new clone of cells
mutations must be of particular types in particular genes
mutations in 3 specific kinds of genes promote cancer
genes that: regulate the cell cycle
terminate a cell’s life
protect DNA against mutation
genes that regulate the cell cycle
stimulate or repress cell growth
genes that terminate a cells life
apoptosis genes
genes that protect DNA against mutation
genes for DNA lesion repair
3 other genetic causes of cancer
chromosome rearrangements
disruption of epigenetic programs
interference by viral genomes
3 possible cellular decisions at checkpoints
GO: proceed to next stage of cell growth
STOP: pause until further notice
DIE
gene names for possible cellular decisions
GO: proto-oncogenes
STOP: tumor suppressor genes
DIE: apoptosis genes
proto-oncogenes
stimulate cells to grow
if a mutation causes overactivity: oncogene, helps cause cancer
if a mutation inactivates a proto-oncogene: cannot cause cancer
types of proto-oncogenes
membrane signal receptor proteins (growth factors)
cytoplasmic signal transduction proteins (growth factors)
transcription factors for growth genes
how genes cause cell growth
growth factor attaches to membrane signal receptor protein
alters a signal transduction protein
transcription factor in cell is turned on for growth
real examples of proto oncogenes
IGF1: protein growth hormone (insulin like growth factor)
RAS: signal transduction protein
RAS
a family of G-proteins
become oncogenes due to mutations that make them permanently turned on
60% of cancers show a mutation of RAS
4 ways a proto-oncogene becomes an oncogene
translocation or transposition: reconnects a gene to wrong promotor so it’s turned on too much
gene amplification: makes duplicate copies of a gene so too much product is made
point mutation in CRM control element: turns up gene expression too high
point mutation in protein coding region: new version of protein with too strong an effect
tumor suppressor genes
15 kinds
many stop cells from dividing
biological functions of tumor suppressor genes
repress genes needed for cell growth
halt cell cycle to repair DNA damage
promote or cause apoptosis
promote cell adhesion
p53 guardian of the genome
DNA-binding protein with 4 subunits
multifunctional transcription factor that turns on genes that shut down the cell cycle
stops cells at G1/S, intimate DNA repair, cause apoptosis
p53 found non-functional in __ to __% of tumors
50-60%
retinoblastoma gene
when both RB alleles are knocked out in a single retina cell you get retinoblastoma
apoptosis
several pathways controlled by mitochondria
dominant and recessive tumorigenic effects
proto-oncogenes: dominant (gain of function)
tumor suppressor genes: recessive (loss of function)
apoptosis: recessive (loss of function)
ECM and cancer
tissues are organized by ECM
it has regulatory functions in normal development and differentiating cells
contact inhibition
cells stop growing when they are touching other cells
monolayer forms then they stop growing
cancer and contact inhibition
cancer cells do not respond to contact inhibition
form multiple layers of cells
telomeres and cancer
embryonic stem cells can regenerate their own telomeres
cancer cells have their own telomerase and can divide an unlimited number of time (no Hayflick limit)
Hayflick limit
number of generations a cell can go through before telomeres are too short
familial cancer
inherited tendency to cancer
xeroderma pigmentosa
can’t go out in sun (UV) light
mutation in base dimer excision repair systems
hereditary nonpolyposis colorectal cancer
mutations in DNA mismatch repair system
tumor suppressor lesion repair gene
BRCA1 & BRCA2
genes involved in DNA regular, repair, and apoptosis
mutations increase risk for breast, ovarian, and prostate cancer
chronic myelogenous leukemia and the Philadelphia chromosome
P chromosome result of reciprocal translocation btw chromosomes 9 and 22 (must happen at specific breakpoints)
causes CML 4,500 cases and 2,400 deaths
ABL1 and BCR in CML
ABL1: growth regulation on chromosome 9
BCR: signal transduction on chromosome 22
fusion of these genes causes expression of growth (ABL1) whenever BCR is used
causes white blood cells grow uncontrollably
acute promyelocytic leukemia
reciprocal translocation of chromosomes 15 and 17
anti cancer molecules
block specific signal transduction proteins
Gleevec and Sutent inhibit tyrosine kinases
DCA (dichloroacetic acid) restores normal apoptosis to cancer cells
can’t stop all cells from having a mutant gene, but we can stop…
genes from being expressed sometimes
