Tumor suppressor genes Flashcards
APC
Inhibitor of mitogenic signaling pathway
“Gatekeeper of colonic neoplasia”
APC = Adenomatous polyposis Coli
Protein: Adenomatous polyposis Coli protein
Func: Inhibitor of WNT signaling
Familial syndrome: Familial colonic polyps and carcinomas
Sporadic cancers: Carcinomas of stomach, colon, pancreas; melanoma
NF1
Inhibitor of mitogenic signaling pathway
Protein: Neurofibromin-1
Func: Inhibitor of RAS/MAPK signaling
Familial syndrome: Neurofibromatosis type I (neurofibromas and malignant peripheral nerve sheath tumors)
Sporadic cancers: Neuroblastoma, juvenile myeloid leukemia
NF2
Inhibitor of mitogenic signaling pathway
Protein: Merlin
Func: Cytoskeletal stability, Hippo pathway signaling
Familial syndrome: Neurofibromatosis type 2 (acoustic schwannoma and meningioma)
Sporadic cancers: Schwannoma, meningioma
PTCH
Inhibitor of mitogenic signaling pathway
Protein: Patched
Func: Inhibitor of hedgehog signaling
Familial syndrome: Gorlin syndrome (basal cell carcinoma, medulloblastoma, several benign tumors)
Sporadic cancers: Basal cell carcinoma, medulloblastoma
PTEN
Inhibitor of mitogenic signaling pathway
Protein: Phophatase and tensin homologue
Func: Inhibitor of PI3K/AKT signaling
Familial syndrome: Cowden syndrome (variety of benign skin, GI, and CNS growths; breast, endometrial and thyroid carcinoma)
Sporadic cancers: Diverse cancers, particularly carcinomas and lymhpoid tumors
SMAD2, SMAD4
Inhibitor of mitogenic signaling pathway
Protein: SMAD2, SMAD4
Func: Component of the TGFB signaling pathway, repressors of MYC and CDK4 expression, inducers of CDK inhibitor expression
Familial syndrome: Juvenille polyposis
Sporadic cancers: Frequently mutated (along with other components of TGFB signaling pathway) in colonic and pancreatic carcinoma
RB
Inhibitor of Cell Cycle Progression
Protein: Retinoblastoma protein
Func: Inhibitor of G1/S transition of cell cycle progression
Familial syndrome: Familial retinoblastoma syndrome (retinoblastoma, osteosarcoma, other sarcomas)
Sporadic cancers: Retinoblastoma; osteosarcoma, carcinomas of breast, colon, lung
CDKN2A
Inhibitor of Cell Cycle Progression
Protein: P16/IKN4a and P14/ARF
Func: P16 = negative regulator of cyclin-dependent kinases; P14 = indirect activator of p53
Familial syndrome: Familial melanoma
Sporadic cancers: Pancreatic, breast and esophageal carcinoma, melanoma, certain leukemias
VHL
Inhibitor of “Pro-Growth” Metabolism and angiogenesis
Protein: Von hippel lindau protein
Func: Inhibitor of hypoxia-induced transcription factors (ex. HIF-1alpha)
Familial syndrome: Von hippel lindau syndrome (cerebellar hemagioblastoma, retinal angioma, renal cell carcinoma)
Sporadic cancers: Renal cell carcinoma
STK11
Inhibitor of “Pro-Growth” Metabolism and angiogenesis
Protein: Liver kinase B1 (LKB1) or STK11
Func: Activator or AMPK family of kinases; suppresses cell growth when cell nutrient and energy levels are low
Familial syndrome: Peutz-Jeghers syndrome (GI polyps, GI cancers, pancreatic carcinoma and other carcinomas)
Sporadic cancers: Diverse carcinomas
SDHB, SDHD
Inhibitor of “Pro-Growth” Metabolism and angiogenesis
Protein: Succinate dehydrogenase complex subunits B & D
Func: TCA cycle, oxidative phosphorylation
Familial syndrome: Familial paraganglioma, familial pheochromocytoma
Sporadic cancers: Paragangloima
CDH1
Inhibitor of Invasion and Metastasis
Protein: E-cadherin
Func: Cell adhesion, inhibition of cell motility
Familial syndrome: Familial gastric cancer
Sporadic cancers: Gastric carcinoma, lobular breast carcinoma
TP53
Enablers of Genomic Stability
Protein: p53
Func: Cell cycle arrest and apoptosis in response to DNA damage
Familial syndrome: Li-Fraumeni syndrome (diverse cancers)
Sporadic cancers: Most human cancers
BRCA1, BRCA2
DNA repair factors
Protein: BRCA-1 & BRAC2 proteins
Func: Repair of double stranded breaks in DNA
Familial syndrome: Familial breast and ovarian carcinoma; carcinomas of male breast; chronic lymphocytic leukemia (BRCA2)
Sporadic cancers: Rare
MSH2, MLH1, MSH6
DNA repair factors
Protein: MSH2, MLH1, MSH6
Func: DNA mismatch repair
Familial syndrome: Hereditary nonpolyposis colon carcinoma
Sporadic cancers: Colonic and endometrial carcinoma
