Term
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Definition
promotes apoptosis by antagonizing bcl-2
p53-deficient tumors |
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Term
*bcl-2*
-function
-oncogene type
-reason for activation |
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Definition
function: mitochondrial protein
oncogene type: inhibits apoptosis
translocation(14:18)
Inhibits apoptosis via mitochondrial pathway
B-cell follicular lymphoma
t(14:18) w/ IgH |
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Term
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Definition
Binds to CDK4 to phosphorylate Rb allowing G1 -> S
mantle cell lymphoma
t(11:14) w/ IgH |
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Term
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Definition
Inhibits MDM2 activity, increasing p53
colon, stomach cancers
silenced by methylation |
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Term
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Definition
competes with Cyclin D for CDK4 binding, prevents Rb phosphorylation
familial melanomas (20%), pancreatic adenocarcinoma (50%), cervix, esophagus
silenced by methylation |
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Term
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Definition
inhibits cyclin D/CDK4 binding (G1->S), induced by p53
inhibits phosphorylation of Rb
P53-deficient tumors
Cip/Kip family |
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Term
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Definition
Inhibits cyclin D/CDK4 binding (G1->S), induced by TGF-beta
TGF-B-deficient tumors
Cip/Kip family |
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Term
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Definition
encodes p27 for cell-cycle inhibition
endometrial carcinomas, glioblastomas
phosphatase/tensin homologue, del. 10q23 |
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Term
*Rb*
-what kind of gene is it?
-mechanism of action?
-associated cancers?
-how does it get damaged? |
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Definition
"prime ex of tumor suppressor gene"
Binds E2G transcription factor preventing G1->S transition via histone deactylase
regulates G1->S, sequesters TFs
Must be *phosphorylated* (inactivated), release E2G TF to allow cyclin D/CDK4 binding
Retinoblastoma, osteogenic sarcoma, many tumors
deletion at *13q14.1*, autosomal dominant (40%), sporadic (60%) from simian virus 40, *HPV E7*, spontaneous mutation |
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Term
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Definition
WNT signal transduction for fate, adhesion, polarity during embryonic dev.; binds E-cadherin in cytoplasm
stomach, colon, pancreas; melanoma, *hepatoblastoma*, hepatocellular carcinoma |
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Term
|
Definition
cell-cell homotypic adhesion in epithelial tissue
stomach carcinoma
down-regulation allows invasion into ECM |
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Term
|
Definition
sense double-strand *DNA breaks*, phosphorylates p53
ataxia telangectasia, many tumors
sensitivity to ionizing radiation, ROS |
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Term
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Definition
*homologous recombination* of double-stranded breaks, bind to RAD51 and G1->S components
80% of *familial breast cancer* (<3% total)
Fanconi anemia (as FancD1)
BRCA1 co-activates estrogen/androgen receptor; functions in DNA repair |
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Term
|
Definition
mismatch repair, failure of DNA repair -> DNA instability
hereditary non-polyposis colon cancer (HNPCC)
autosomal dominant, may be methylated
microsatellite (tandem repeat) instability |
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Term
|
Definition
nucleotide excision repair
Xeroderma pigmentosum, skin cancers
-XP: AR, inherited inability to repair UV-induced DNA damage, 2000x i/c risk of skin cancer
sensitivity to UVB radiation |
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Term
|
Definition
encodes hepatocyte growth factor
follicular *thyroid* cancer
growth-stimulatory autocrine loop |
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Term
|
Definition
Encodes fibroblast growth factor (FGF)
stomach cancer |
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Term
|
Definition
encodes fibroblast growth factor
bladder, breast cancer; melanoma |
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Term
|
Definition
encodes PDGF beta-chain
astrocytomas, osteosarcomas
a.k.a. Simian sarcoma virus proto-oncogene |
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Term
|
Definition
encodes type 2 TGF-beta
HNPCC (70%)
TGF-beta inhibits cellular proliferation via p27 |
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Term
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Definition
encodes TGF-beta inhibitory signal transduction
pancreatic cancer (50%) |
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Term
|
Definition
TGF normally inhibits cell proliferation; if you release TGF, you can't inhibit proliferation. Normally suppresses tumors and inhibits CDKs
induced proliferation by binding to EGF receptors
astrocytomas, hepatocellular carcinomas |
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Term
|
Definition
ubiquitin ligase, regulates VEGF, PDGF
hereditary renal cancer (clear cell), pheochromocytoma, angiomas
mutation in von Hippel Lindau gene on chr 3; silenced by methylation |
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Term
|
Definition
encodes colony-stimulator factor (CSF)-1 receptor
myeloid leukemias
point mutation |
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Term
|
Definition
receptor for stem-cell factor
constitutive activation of tyrosine kinase
stromal tumors in GI tract
point mutation |
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Term
|
Definition
receptor for epidermal growth factor
squamous carcinoma of lung (80%), glioblastomas (50%), head/neck tumors (80-100%) |
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Term
|
Definition
receptor for EGF, a.k.a. human EGFR 2 (HER2, Neu)
breast cancer (25%), adenocarcinomas of ovary
treated with monoclonal antibody (herceptin) in targeting therapy |
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Term
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Definition
encodes glial cell-derived neurotropic factor receptors (RET)
MEN = multiple endocrine neoplasia
medullary thyroid carcinoma; adrenal, parathyroid tumors, Hirschsprung's
point mutation in RET extracellular domain |
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Term
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Definition
Encodes RET
thyroid, adrenal tumors, Hirschsprung's
point mutation in RET cytoplasmic domain |
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Term
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Definition
encodes PDGF receptor
myelomonocytic leukemia, gliomas
t(12:9) |
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Term
*Abl*
-function
-oncogene type
-reason for activation
-how does its associated mutation work?
-associated cancers |
|
Definition
function: tyrosine kinase
oncogene type: signal transduction
translocation
forms chimeric protein with BCR (bcr-abl) resulting in constitutive activation
CML
t(9:22, *Philadelphia) w/ BCR -> leukemia* |
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Term
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Definition
down-regulates *beta-catenin*
decreases adhesion, GF signals
WNT signal transduction controls cell fate, adhesion, polarity in embryo and hematopoietic stem cells
*Adenomatous polyposis coli,* non-familial colorectal cancers (70-80%), hepatocellular carcinoma
No APC -> colon polyps form in children
point mutations in APC (5q21), beta-catenin gene |
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Term
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Definition
*P450*-dependent monochrome oxidase in liver
lung cancer
polymorphism: 7x risk lung cancer in whites |
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Term
|
Definition
encodes neurofibromin, *GTPase-activating* protein (GAP!!)
neurofibromatosis type 1
*deficiency locks RAS in active state*
can't augment GTPase activity of RAS |
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Term
|
Definition
encodes merlin, binds actin/CD44 for adhesions
neurofibromatosis type 2 (Schwannomas) |
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Term
*Ras*
-function
-oncogene type
-reason for activation
-what does it activate?
-associated tumors?
-codons |
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Definition
function: GTP binding
oncogene type: signal transduction
point mutation
activates MAP-kinase pathway
many tumors (15-20%)
*lung, bladder* cancer
constitutive due to loss of GTPase activity
most common abnormality of dominant oncogenes (codons 12, 59, 61) - three positions in ras where if changes occur, give rise to mutations
mutations in RAS result in inability of GAP to stimulate GTPase activity of RAS |
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Term
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Definition
causes transcription
Transcriptional activation, induced when quiescent cells receive signal to divide, d/c adhesion
*Burkitt's* (B-cell) lymphoma, many tumors
t(8:14)
c-myc
EBV, t(8:14) w/ IgH -> i/c in myc protein & DNA transcription
t(8:2) or (8:22) w/IgL |
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Term
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Definition
transcription factor
includes TGF-B genes, *p21*
prostate cancers (70%) |
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Term
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Definition
transcriptional activation
d/c adhesion
small cell cancers of the *lung* |
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Term
|
Definition
transcriptional activation
d/c adhesion
neuroblastomas
results from gene amplification
cytogenetically is distinct b/c of double minutes (little dna pieces) |
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Term
|
Definition
transcriptional activation of genes in renal diff.
*Wilms tumor* (pediatric kidney cancer)
mutation on 11p13 |
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Term
p53
-function
-oncogene type
-reason for activation
-"job description" |
|
Definition
*function: GTP binding*
oncogene type: signal transduction
reason for activation: point mutation
located on 17p13.1
most common target for genetic alteration in human tumors (>50%)
functions to arrest cell cycle, initiate apoptosis in response to cell damage by controlling the transcription of other genes
molecular policeman of the cell cycle
up-regulates p21 (a CDKI)
up-regulates BAX |
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Term
|
Definition
deleted in colon carcinoma
18q21
often deleted in colon and rectum carcinomas
possibly a tumor suppressor gene
(contrast with APC gene) |
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Term
| what must happen in order for the cell cycle to progress beyond the G1/S checkpoint? |
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Definition
GF binding -> i/c cyclin D
cyclin D binding CDK4
cyclin D/CDK4 ("MPF") *phosphorylates Rb*
phosphorylated Rb releases EF2
EF2 participates in gene transcription |
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Term
| translocation mutation in ALL, Philadelphia chromosome (CML) |
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Definition
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