Nelson Molecular basis of Neoplasia Flashcards
Four classes of normal regulatory genes that are the principal targets of cancer causing mutations?
- growth promoting proto-oncogenes
- growth inhibiting tumor suppressor genes
- genes that regulate apoptosis
- genes involves in DNA repair
Mutation that contributes to the development of malignant phenotype?
Driver mutation
Mutations that have no phenotypic consequence?
Passenger mutations
8 Hallmarks of Cancer:
- Self-sufficiency in growth signals
- Insensitivity to growth inhibitory signals (inactivation of tumor suppressor genes)
- Altered cellular metabolism (the Warburg effect)
- Evasion of apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Ability to invade and metastasize
- Ability to evade host immune response
t(9;22) translocation on ABL gene associated with:
CML
Amplification of HER 2/neu associated with:
Breast carcinoma (marker of aggressiveness)
25% of breast cancers overexpress HER-2/neu
Point mutation in RAS associated with:
Leukemia
Lung, colon, pancreatic carcinomas
BRAF mutation associated with:
melanomas
KIT mutation associated with:
GI stromal tumors
activation of tyrosine kinase receptor c-KIT
KRAS mutations are found in 40% of:
Colorectal cancer
Amplification of N-MYC = ?
neuroblastoma
Detection of ________ fusion is diagnostic of CML.
BCR-ABL
EGFR activating mutation and rearrangement of ALK direct therapy in___________.
lung adenocarcinoma
JAK2 tyrosine kinase mutations = ?
Myeloproliferative disorders
Difference between Tumor suppressor genes and oncogenes with respect to growth inhibition?
Tumor suppressor genes require both alleles to be knocked out: “two hit” hypothesis
APC is a ____________ associated with ________.
tumor suppressor gene
colorectal carcinoma
BRCA1/BRCA2 regulates ___________ and is associated with ________________.
DNA repair
breast, ovary, prostate carcinoma
“molecular policeman” that prevents propagation of genetically damaged cells:
p53
**most frequently mutated gene in human cancers
Aerobic glycolysis in cancer cells is known as:
The Warburg effect
**visualized on PET scan with 18F-fluorodeoxyglucose
Anit-apoptotic gene product that protects lymphocytes. Overexpressed due to t(14;18) translocation in 85% of B-cell lymphomas:
BCL2
**involved in intrinsic (mitochondrial) pathway
BCL2 positive lymph node follicles stain?
dark brown
Maintenance of ____________ by ___________ gives cancer cells limitless proliferative potential by evading mitotic crisis.
telomeres, upregulated telomerase
Key angiogenic promoter:
VEGF
Cell mediated immunity is the dominant anti-tumor mechanism. Which cells are involved?
CD8s, NKs, Macs