Term
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Definition
Loss of function. Recessive.
TP53:Master break,activated by DNA damage. Arrests cell cycle through P21
Inhibits cell cycle when phosphorylated
RB: Phosphoprotein. When hypophosphorylated Binds E2F stops cell cycle. Can be downregulated by miRNA |
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Term
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Definition
Gain of Function(Dominant)
Anything that promotes cell division
ERB-B2/HER2 codes for EGFR2. Breast and ovary cancer.
BCR-ABL: codes for TK. Involved in CML |
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Term
| CML - Phladelphia chromosome |
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Definition
t(9:22) -> ABL:BCR fusion protein.
Constitutive tyrosine kinase activity. |
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Term
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Definition
Metabolize before reacting with DNA
Benzo-a-Pyrene(tobacco): forms DNA adducts(DNA covalently bonded to chemical). Converted to BPDE
Aflatoxin B1: Liver cancer. Asperigillus flavus mold on grain and peanuts.
CYP450 converts aflatoxin into epooxide forms adduct. |
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Term
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Definition
Burkitss lymphoma(jaw tumur) EBV(mono)
HIV: Kaposi's sarcoma and lymphoma(EBV)
HPV: Cervical Cancer. E6 blocks p54
E7 blocks Rb.(makes cyclin E) |
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Term
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Definition
Multiple endocrine neoplasia type2(men2)
Famililial cancer syndrome. AD
Gain of function mutation: RET.(RTK onstitutive activation)
Hereditary Papillary renal Carcinoma
MET(HGFR) mutation(hepatocyte growth factor)
MET involved in embryonic development and wound healing |
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Term
| Oncogene activation in Sporadic Cancer |
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Definition
RAS(GTPase) activation(signal transducer)
20% of sporadic cancer
MYC activation: translocation in burkett. Amplified in breast, colon, lung. Increased cell proliferation(cyclin d) |
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Term
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Definition
T(8;14)
MYC(overexpressed) placed under control of strong Ig promoter. |
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Term
CML(Chronic myelogenousleukaemia)
Philadelphia chromosome |
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Definition
T(9;22)
BCR-ABL fusion protein(constant TK activity)
Chronic Phase: 3 yr survival
Blast Phase: few months
Imatinib / Gleevac(BCR-ABL TK inhibitor) Only fusion protein. |
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Term
| Acute promyelocytic Leukaemia(APL) |
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Definition
T(15;17)
Fusion PML-RARa. Retinoic acid receptor(Nuclear receptor and TF)
PML_RARa protein converted to a repressor turning off genes needed for myeloid differentiation and promoting prolonged proliferation |
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Term
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Definition
T(11;22)
EWS-FLI1 FUsion.
Small round tumors of bone and soft tissue. |
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Term
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Definition
N-MYC amplification.
Extra chromosomal double minutes(small
fragments of extrachoromosomal DNA that
can be reincorporated)
Tumors of adrenal medulla or sympathetic chain ganglia. |
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Term
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Definition
RB1 mutation
White reflex:leucokoria.(White eye)
Rb normally binds and inhibits E2F and prevents grwoth pathway. |
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Term
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Definition
P53 mutation. AD. LOF.
Highly variable phenotype(where 2nd hit occurs)
Damged cells survive and proliferate |
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Term
| Neurofibromatosis type 1(NF1) |
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Definition
50% sporadic. AD complete penetrance by 5
Extremely variable.
Lisch nodules. Freckles, cafe au lait spots
NF1(RAS GAP) inactivates p21 Ras proto-oncogene. Mutated = prolonged activation
of RAS(GF receptor) |
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Term
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Definition
Care taker TSG mutation:BRCA1 and BRCA2
Involved in DNA repair.
Also involved in ovarian and prostate cancer |
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Term
| Famililial adenomatous polyposis(FAP) |
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Definition
APC mutation.
APC binds to B-catenin.
B-catenin causes cell proliferation.(activates myc).
Many Polyps |
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Term
Hereditary non-polyposis colon-carcinoma
HNPCC |
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Definition
Mutation in DNA repair genes. MLH, MSH
TGFBR2 mutated in 70% of HNPCC. Normally involved in growth inhibitory
signaling pathway.
Replication slippage, microsatelllite instability. Replication error positive
(RER phenotype)
No polyps |
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Term
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Definition
TGFBR2: HNBCC and RER+
SMAD4(pro-apoptotic: 50% pancreatic
cancer.
PTEN: Cell cycle arrest, apoptosis.
Prostate cancer
WT-1: Wilms tumor, pediatric kidney
cancer |
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Term
| Xeroderma Pigmentosa (XP) |
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Definition
AR
Nucleotide excision repair.
Pyrimidine dimers not repaired |
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Term
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Definition
Oculocutaneous telangiectasia (dilated
vessels in eye, ear.
Mutation of ATM. Defect in DNA repair by
homologous recombination. |
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Term
Bloom SYndrome
Werner Syndrome |
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Definition
BLM= DNA helicase.
SUnsensitivity, sister chromatid exchange
WRN = DNA helicase and exonuclease
Patients have shorter telomeres. Age
prematurely. |
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Term
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Definition
Most common and aggressive brain tumor
100x expression of miRNA in glioblastoma multiforme. |
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