Genetic Origins of Cancer Flashcards
oncogenes are..
genes that have acquired the ability to induce normal characteristics of cancer cells
A normal oncogene is called…
a proto-oncogene
2 characteristics of tumor suppressor genes
- cellular brakes
- cannot arrest proliferation when mutated
list the 6 hallmarks of cancer
- self-sufficiency in growth signals
- insensitivity to antigrowth signals
- evasion of apoptosis
- limitless replicative potential
- sustained angiogenesis
- tissue invasion and metastasis
the concept of endogenous retroviruses were modeled in
the 1970s
the concept of endogenous retroviruses attempted to explain
how tumor viruses might initiate numerous cancers that showed no symptoms of viral infections
Have endogenous proviruses been acquired in germs lines of both humans and mammals?
no, just in mammals
name a virus that has the potential to cause cancer
HPV virus
what is the mechanism of viruses that cause cancer?
insertion of a viral oncogene or induction of tissue damage
explain the translocation of the Philadelphia chromosome
exchange between ABL gene in chromosome 9 w/ the BCR gene in chromosome 22
which chromosome is known as the Philadelphia chromosome?
shortened chromosome 22
the gene product of the philadelphia chromosome leads to the development of what cancers
leukemias
list 3 other types of DNA arrangements
- deletion/ insertion
- transpositions
- inversion
how do ras mutants result in an active protein
by not being able to carry out GTP hydrolysis
what does MAPK stand for
mitogen-activated protein kinase
EGF signal transduction is characterized by what 4 characteristics
- GF binding
- receptor dimerization, cross phosphorylation
- activation of internal kinase cascade
- transcription/ gene expression
explain how a truncated receptor leads to deregulated growth factor signaling
emits signals even in the absence of ligand binding
what growth factor is suspected in autophosphorylation
EGF
what GF is dimerized by a heparin link
FGF2
what single molecule simultaneously contacts 2 receptor monomers causing dimerization?
EPO (erythropoietin)
what ligand molecules may bind 2 monomeric receptors exposing 2 activation sites?
TGFa
what is the effect of GF on platelet cells
when activated the secretory vessels containing GF fuse with PM and release mitogens
TRK oncogene is a…
chromosomal inversion on the same chromosome (fusion gene)
fusion gene of the TRK oncogene causes the
receptor region to remain dimerized and its kinase becomes constitutively activated
STAT stands for
signal transduction and activation of transcription
in what pathway of cell proliferation is the kinase not built into the receptor?
the Jak-STAT pathway
list the 5 different types of abnormalities that can result in proto-oncogenes
- point mutation
- gene amplification
- chromosomal translocation
- local DNA arrangements
- insertional mutagenesis (viral DNA)
ras oncogenes differ from their proto-oncogenes by point mutations resulting in…
single substitutions at critical positions where Gly is changed for Val
what act as brakes that slow down cell cycle progression?
proteins encoded by tumor suppressor genes
what is known as the prototype of a tumor suppressor gene?
Rb
what is the target of tumor suppressor genes that is often mutated in a number of different human tumors?
cyclin D/ Cdk4,6
b/c a single oncogene is requires to produce cancer oncogenes are characterized as
exhibiting dominant behavior
with tumor suppressor genes _____ copies must become ________ becoming _____ and leading to _____.
both
non-functional
recessive
cancer
when active Rb binds to E2F transcription factor it prevents:
-transcription of genes for DNA replication
- passage from G1 into S phase
a phosphorylated Rb can NOT bind to E2F causing…
- E2F to activate gene transcription (onto S phase)
- dephosphorylated Rb returns to inhibit E2F
what type of experiments demonstrate that cancer is of a recessive phenotype
cell fusion experiments
explain a cell fusion experiment
a cancer and normal cell are fused the fused cell divides and the new nuclei contains chromosomes from original cells. results in a hybrid cell w/ normal growth. hybrid cell divides and chromosomes are lost resulting in a cancer cell w/ uncontrolled growth
in a cell fusion experiment reversion of the cancer phenotype is due to..
the loss of tumor suppressor genes
what are the 2 different types of inheritance patterns of mutation genes?
recessive cancer-risk syndrome
dominant cancer-risk syndrome
in recessive cancer-risk syndrome…
2 copies of tumor suppressor genes must be inherited to create a high risk of developing cancer
in dominant cancer-risk syndrome
a single defective tumor suppressor gene is sufficient to cause high risk of getting cancer, but a second gene is required before cancer can actually arise
what allows for functional tumor suppression?
heterozygosity
what is loss of heterozygosity?
when a normal chromosome becomes disrupted bc of the mutated chromosome
list the 3 types of loss of heterozygosity
- mitotic nondisjunction
- mitotic recombination
- gene conversion
explain mitotic nondisjunction
duplicate copies of the normal chromosome fail to divide at the time of mitosis causing both copies to go into one cell and the other cell is left with the mutated chromosome
explain mitotic recombination
2 homologous chromosomes exchanging DNA sequences when lined up during mitosis causing 2 mutant copies of the tumor suppressor gene to end up in the same cell
explain gene conversion
base sequence information getting copied from one chromosome to another when they’re lined up next to each other. causes the mutant tumor suppressor gene to be copied onto the normal chromosome
explain hereditary Rb
offspring have a 50% chance of inheriting a defective Rb gene
explain nonhereditary Rb
cancer only arises if both copies of Rb undergo mutations in the same cell
Rb tumors are believed to arise from a
multipotent stem cell precurser of multiple types of cells
name a type of human tumor suppressor genes that have been cloned
RB
NF1
NF1 is a _____ ______ of Ras signaling
negative regulator
NF1 stands for
neurofibromatosis type 1
neurofibromatosis type 1 is a
familial cancer precursor w/ an inherited mutant allele
what forms around the cell sheaths of PNS?
neurofibromas form around cell sheaths of the PNS
NF1 patients are at higher risk for
developing additional cancers
what drives more than a quarter of breast cancers
missing gene
