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70 Cards in this Set

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oncogenes [protooncogenes] are derived from normal cell genes involved in {3}
normal growth, repair, entering cell cycle
oncoproteins usually affect
signaling transduction pathways (ie. GF, GF-R, signal transduction proteins, nuclear regulatory, cell cycle regulators) --> second messenger --> nuclear transcription
impt proto-oncogene involved in astrocytomas and osteosarcomas (name type of protein)
c-sis
PDGF / PDGF-R
oncogenes that are homologs of FGF
hst-1
int-2
overexpressed in stomach cancer
hst-1 (FGF homolog)
amplified in bladder, breast ca, hepatocellular carcinoma
int-2 (FGF homolog)
ras (oncogene) causes overexpression of __(1)__ which is related to __(2)__ which is expressed in __(3)__ and __(4)__
1. TGF-a
2. EGF
3. astrocytoma
4. hepatocellular ca
involved in follicular thyroid cancer {2}
HGF = hepatocellular growth factor
c-met = HGF receptor
several oncogenes encode GF-R that are
always on - even w/o binding of ligand
RET protooncogene = receptor for ___ expressed in ___
glial cell line-derived neurotrophic factor with tyrosine kinase activity;
neuroendocrine cells of the thyroid, adrenal medulla and parathyroid
point mutation of RET assoc w/
MEN 2A and 2B and familial medullary thyroid carcinoma [c-cells secrete calcinotin]
Somatic rearrangement of RET assoc w/
sporadic papillary carcinoma
point mutation in fms which encodes ___ leads to ___
CSF-1, myeloid leukemia
overexpressed in 80% of SCC of lung and less commonly in carcinomas of bladder, GI tract and astrocytomas
erb-b1 (EGFR)
amplified in adenocarcinoma of the breast, ovary, lung, stomach and salivary gland
erb B2 (Her2-neu)
receptor for stem cell steel factor
kit, involved in GI and other soft tissue tumors
single most common abnormality of dominant oncogenes in human tumors
ras (GTP protein)
Non receptor associated tyrosine kinase
c-abl
nuclear regulator protein oncogenes
myc, myb, jun, fos
most common nuclear regulator protein involved in human cancers (breast, lung, colon, etc)
myc
N-myc amplification is seen with
neuroblastoma, and small cell carcinoma of lung
C-myc is involved in what translocation and disease?
Burkitts lymphoma t(8,14)
L-myc amplication seen in
small cell carcinoma of lung
cyclin and cyclin dependent kinases (CDK)'s do what?
force quiescent cells to enter cell cycle
mut in genes that encode ____ are implicated in several human cancer
cell cycle regulators (cdk-i, etc)
cyclin gene overexpressed in many cancers (breast, esophagus, liver, translocated in subset of lymphomas -- mantle cell lymphomas)
Cyclin D
amplification of ___ noted in glioblastoma, melanoma and sarcomas
cdk4
tumor suppressors - name the molecules that regulate nuclear transcription and cell cycle
Rb, p53, WT-1, p16 (INK4a), KLF6, BRCA-1, BRCA-2
location of Rb
13q14
job of Rb
regulate cell cycle
Knudson's 2 hit theory:
somatic mut of Rb
inherited mut in Rb in all somatic cells (2nd hit in retinal cell)
Knudson's 2 hit theory:
sporadic case of Rb
both mut occur sporadically in single retinal cell
Rb is found in all cells.
Active form?
Inactive form?
active: underphosphorylated
inactive: hyperphosphorylated
fxn of active Rb
prevent G1 --> S transition
binds/sequesters E2F (TF)
p53 - chromosome location. __% of tumors have a mut in p53
17q13.1
over 50% human tumors have mut
p53 fxn
cell cycle arrest in response to DNA damage -- prevents propagation of genetically damaged cells
tumors assoc w somatic mut in p53
breast, lung, colon
tumors assoc w/ inherited mut in p53
Li Fraumeni Syndrome
multiple carcinomas (breast, brain)
sarcomas
p53 binds ___ and ____
binds DNA and stimulates transcription
2 major effects of p53
1. arrest of cell cycle (cdki p21)
2. apoptosis (Bax)
what can stimulate the activation of normal p53
hypoxia
p53 can be inactivated by
transforming proteins of DNA virus, E6 of HPV (bind and degrade p53)
therapeutic implications of p53
chemo and radiation therapy cause DNA damage tumor cells with normal P53 gene are more likely to respond to this therapy, than tumors that carry the mutant gene.
WT
location:
fxn:
dz assoc:
chromosome 11p13
nuclear transcription
Wilms tumor (nephroblastoma)
p16 (INK4a)
fxn:
dz assoc
cell cycle regulation via cdki
somatic: pancreatic, breast, esophageal
inherited: malignant melanoma
KLF6
fxn:
dz assoc:
encodes TF
mut in more than 70% of primary prostate cancer
APC
fxn:
dz assoc (somatic/familial)
inhibition of signal transduction, downregulates b-catenin
somatic: carcinoma of stomach, colon, pancreas, melanomas
familial: FAMILIAL ADENOMATOUS POLYPOSIS COLI / COLON CANCER
PTEN
location:
fxn:
dz assoc
Phosphatase and tensin homolog, located on chromosome 10q23
cell cycle arrest and apoptosis - p27 Cip/Kip
endometrial and prostate cancer
SMAD 2 and SMAD 4 (DPC4)
fxn:
dz:
TGF-β growth inhibitory signal transduction
SMAD 4 is inactivated in 50% of pancreatic cancers
SMAD2 is present in some colorectal cancers
NF-1 protein product
neurofibromin
NF1 fxn:
dz assoc:
inhibit RAS signal transduction
inhibits p21 (cell cycle inhibitor)
NF2 protein product
merlin
NF2 fxn:
dz:
cytoskeleton stability
somatic: schwannomas, meningiomas
familial: Neurofibromatosis type II, acoustic schwannomas and meningiomas
TGF-β receptor
fxn
dz assoc
growth inhibition
somatic: carcinoma of colon
E-cadherin
fxn
dz assoc
adhesion
somatic: stomach carcinoma
inherited: familial gastric cancer
Bcl-2
location
fxn
18q21
overexpression = evade apoptosis, survive long period of time, accumulate B-lymphocytes resulting in lymphadenopathy and marrow infiltration
85% of ______ carry a characteristic t(14;18)(q32;q21) translocation which prevents apoptosis
follicular B cell lymphomas
fused w/ Ig-H (heavy chain) 14q32
Bcl-2 family
apoptotic members:
antiapoptotic members:
apop: bak, BAX, bim

anti-apop: bcl-2, bcl-x
mismatch repair
mut in:
dz:
Germ line mutation of MSH2 (2p16) and MLH1 (3p21) account for 30% of cases.
Hereditary Nonpolyposis Cancer Syndrome
microsatellite instability is hallmark of mismatch repair in
Hereditary Nonpolyposis Cancer Syndrome
Cancers of the cecum and proximal colon (patients are < 50 years), also associated with endometrial and ovarian cancers.
dz assoc w/ mut in NER
xeroderma pigmentosum
(pyr dimers, UV damage)
dz assoc w/ defect in homologus recombination
AR disorders : Ataxia-telangiectasia, Bloom syndrome and Fanconi anemia- increased chance of leukemia lymphoma.
gene mutation involved in Ataxia-telangiectasia
ATM
characteristics of ataxia telangiectasia
Cerebellar ataxia, defective lymphocyte maturation and proliferation
Immunodeficiency, acute sensitivity to ionizing radiation and susceptibility to lymphoid malignancies.
BCRA-1 located
chromosome 17
BCRA-2 location
chromosome 13
Individuals who inherit mutations of BRCA 1 and 2 susceptible to
breast cancer
(10-20% of breast cancers are familial and mutation of BRCA-1 and BRCA-2 account for 80% of familial breast cancer.)
Germ line mutation of BRCA-1
dz involved?
breast and ovarian cancer
Germ line mutation of BRCA-2
dz:
ovary (<BRCA-1) and male breast cancer.
telomeres - how they function
Telomerase shortening is a tumor suppressor mechanism
absent in most somatic cells
adding telomerase would increase life span