Cancer 2 Flashcards
What is the mechanism of oncogenesis?
Proto-oncogene activation -> oncogene
Loss of TS gene expression (loss of fxn)
Proto-oncogene and TS genetics?
P-O: 1 activating mutation, gain of fxn
TS: 2 inactivating mutations, loss of fxn
Ways that oncogenes can be activated?
Regulatory sequence mutation (leading to increase in protein expression)
Gene sequence mutation (constitutively active)
Gene amplification (increase in protein expression)
Chromosome translocation (chimeric gene product, overexpression)
Multiple endocrine neoplasia, type 2 (MEN2)
Gain of function mutation: RET
Loss of function would be Hirschprung dx
RTK, constitutive activation
Affects 2 or more endocrine glands
Hereditary papillary renal carcinoma
Mutation in MET
What type of cx is RAS activation most involved in?
Colorectal cancer
Which 2 tumors are due to translocation events that leads to over-expression of proto-oncogenes?
t(8;14) - Burkitt’s Lymphoma
t(14;18) - Follicular Lymphoma
Which 3 tumors are due to translocation events that create a fusion / chimeric gene?
t(9;22) - Chronic Myeloid Leukemia (CML)
t(15;17) - Acute Promyelocytic Leukemia
t(11;22) - Ewing Sarcoma
Burkitt’s Lymphoma
MYC activation (over-expression of proto-oncogene)
Translocation: t(8;14)
MYC is placed under the control of a strong Ig promoter
Follicular Lymphoma
Bcl-2 is placed under the control of a strong Ig promoter (similar to MYC and Burkitt’s)
Translocation: t(14;18)
Chronic Myelogenous Leukemia
Philadelphia chromosome (BCR-ABL), which results in constantly active tyrosine kinase activity
Translocation: der22 t(9;22)
Tx: Imatinib; is good because this drug specifically binds to the BCR-ABL receptor site, so that the tumor cell does not proliferate
Acute Promyelotic Leukemia
Fusion of PML and RAR alpha (PML-RARa)
Translocation: t(15;17)
Ewing Sarcoma
Fusion of EWS and FLI1
Translocation: t(11;22)
Bones
Neuroblastoma
N-MYC amplification
Presents as a mass in the adrenals
Double minutes in homogeneous staining regions
