Flashcards in CH3 - Principles of Neoplasia Deck (169)
Stem cell growth factor receptor, Point mutation, Gastrointestinal stromal tumor
RAS gene family
GTP-binding protein, Point mutation, Carcinomas, melanoma, and lymphoma
Tyrosine kinase T(9;22) with BCR CML and some types of ALL
What are the nuclear regulators?
C-MYC, N-MYC, L-MYC
Transcription factor, t(8;I4) involving IgH, Burkitt lymphoma
Transcription factor, Amplification, Neuroblastoma
Transcription factor, Amplification, Lung carcinoma (small cell)
CCND1 (cyclin D1)
Cyclin t(8;14) involving IgH, Mantle cell lymphoma
If DNA repair is not possible, what does p53 do?
How does p53 induce apoptosis?
upregulates BAX, which disrupts Bcl2 leading to cytochrome c leaks from the mitochondria activating apoptosis
Knudson two-hit hypothesis
both copies of the p53 gene must be knocked out for tumor formation, Both copies of Rb gene must be knocked out for tumor formation
Loss of p53 is seen in what percentage of cancers?
>50% of cancers.
p53 Germline mutation results in
Li-Fraumeni syndrome (2nd hit is somatic),
Li-Fraumeni syndrome is characterized by?
the propensity to develop multiple types of carcinomas and sarcomas,
regulates progression from G0 to S phase.
How does Rb regulate the progression to S phase?
holds the E2F transcription factor, which is necessary for transition to the S phase
E2F is released when?
RB is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex
Rb mutation results in
constitutively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells.
(both hits are somatic) and it is characterized by unilateral retinoblastoma
Rb Germline mutation results in
familial retinoblastoma (2nd hit is somatic) and is characterized by bilateral retinoblastoma and osteosarcoma.
What is the function of regulators of apoptosis?
Prevent apoptosis in normal cells, but promote apoptosis in mutated cells whose DNA cannot be repaired (e.g Bcl2)
normally stabilizes the mitochondrial membrane, blocking release of cytochrome c
Disruption of Bcl2 allows what to happen?
Cytochrome c to leave the mitochondria and activate apoptosis
Bcl2 in follicular lymphoma?
it is overexpressed in follicular lymphoma,
Why is Bcl2 overexpressed in follicular lymphoma?
t(14;18) moves Bcl2 (chromosome 18) to the Ig heavy chain locus (chromosome 14), resulting in increased Bcl2.
How is apoptosis inhibited in follicular lymphoma?
Mitochondrial membrane is further stabilized by overexpressed Bcl2, prohibiting apoptosis.
In follicular lymphoma, how does the inhibition of apoptosis lead to lymphoma?
B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center accumulate, leading to lymphoma.
What is necessary for cell immortality?
Normally telomeres do what?
shorten with serial cell divisions, eventually resulting in cellular senescence