Neoplasia Flashcards
Retinoblastoma
increased risk if patient carries RB allele
autosomal dominant
Multiple Endocrine neoplasia
mutation in TK or melanin transcription factors
oncogene
multiple benign colon tumors
Hereditary nonpolyposis colon cancer (HNPCC)
AD disorder caused by mutation in DNA mismatch repair
most common cancer predisposition therapy
**colon (proximal and cecum)
SI, endometrial, and ovarian cancers
Xeroderma pigmentosum
failure of nucleotide excision repair
cells extremely vulnerable to UV damage
increased melanomas (even of the eye)
RET gene mutation
TK receptor becomes oncogenic
constitutively dimerized
cause Multiple Endocrine Neoplasia (MEN)
thyroid, adrenal, para cancers
c-KIT mutations
oncogenic mutation causes permanent dimerization
GI cancers
RAS mutations
RAS oncogene
most common oncogene mutation
pancreatic adenocarcinomas, cholangiocarcniomas
(rare in cervix and breast)
**GTPase gene is mutated (usually inhibits RAS)
RAF mutation
downstream of RAS pathway
melanoma development
Abl mutation
nonreceptor TK oncogene
BCR-ABL complex forms after translocation
Acute Lymphoblastic Anemia
and CML
MYC mutation
oncogenic mutation that pushes the cell thru cycle unchecked
Burkitt Lymphoma
many carcinomas
small cell lung carcinomas
neuroblastoma (indicates poor px)
RB protein
plays a role in the G1/S transition
inactivated by phosphorylation increases cyclin activity
Retinoblastoma
also small cell carcinomas of lung breast and bladder
Li-Fraumeni syndrom
TS
inherited somatic mutation of p53
LOH–> sarcomas and carcinomas (Brain, Breast, Leukemias)
APC/ B-catenin mutations
APC usually inhibits B-catenin (promotes proliferation)
TS
loss of APC or loss of E-cadherins
colon polyps or polyps that become malignant (colorectal carcinoma
INK4a/ARF mutation
usually –>p16–>inhibition of cell replicaiton and increases p53
TS
mutated in a variety of cancers
TGF-B mutation
potent inhibitor of proliferation (activates RB)
100% of pancreatic cancers
83% colon cancers
PTEN mutations
normally inhibits PI3K/AKT pathway
Cowden syndrome and benign epithelial growths
Neurofibromatous type I
defects in neurofibromatin causes RAS overactivation
causes NFI= neurofibromas+ optic nerve nerve gliomas
can give rise to malignant peripheral nerve sheath tumors
von Hippel-Lindau meutations
mutations lead to unregulated HIF activity
increased hereditary renal cell cancers, pheochromocytomas, hemangioblastomas
Wilm’s tumor
mutation in WT1 causes pediatric kidney cancer
GOF mutations cause some cancers in adults
Patched (PTCH) mutation
causes gorlin syndrome and causes inherited nevoid basal cell carcinomas
Bevacizumb
anti-VEGF Ab used to treat a variety of cancers
Human T cell leukemia virus type I
cause T cell leukemia/lymphoma
Japan and Caribbean
d/t initial polyclonal T cell proliferation
HPV
Types 16 and 18 increase risk of squamous cell carcinoma of cervix, anus, oropharynx
inactivate Ts, activate cyclins, inhibit apoptosis
EBV
infects B lymphocytes
can cause Burkitt lymphoma ( Africa and New Guinea)
B cell lymphomas in HIV + patients
Nasopharyngeal cancers
H. Pylori
increase epithelial cell proliferation and chronic inflammation
gastric adenocarcinomas, gastric lymphomas
MALTomas that are cured with antibiotics unless additional mutations have occurred
small cell carcinoma of the lung
often secretes corticotropin and POMC
causes Cushing
squamous cell bronchogenic carcinoma
secretes PTHRP
causes hypercalcemia
Troussseau syndrome
migratory thromboembolism d/t pancreatic lung carcinomas
nonbacterial thrombic endocarditis
fibrous deposition on heard valves seen in mucin secreting adenomas
NF2
mutations in Neurofibromin 2 (Merlin)
causes b/l acoustic schwannomas
