Pathology of Neoplasia (22)

Terms	Definitions
List 3 broad carcinogenic agents.	chemical agents physical agents oncogenic virus bacterial infection
What type of carcinogens require metabolic conversion by cytochrome P450 in the liver?	indirect acting
Review some chemical carcinogens.
Review some major chemical carcinogens.
What are the 2 players in chemical carcinogenesis?	initiator: causes mutation in cell promotor: causes clonal expansion of initiated cells through enzyme activation or by mutation
Name 2 types of radiation that can be carcinogenic.	UV rays ionizing radiation
What 2 factors determine the degree of damage due to UV radiation?	intensit of exposure and quantity
What type of radiation causes DNA damage due to formation of pyrimidine dimers?	UV rays
What is the normal mechanism of repair of pyrimidine dimers?	nucleotide excision repair (NER)
List 3 cancers caused by UV radiation.	squamous cell carcinoma basal cell carcinoma melanoma
List 3 ways in which ionizing radiation is carcinogenic.	DNA damage alters proteins inactivates enzymes injures membranes ionization of macromolecules and generation of free radicals
Most oncogenic viruses have what type of nucleic acid?	DNA
Name 3 major DNA oncogenic viruses.	HPV EBV HBV
Virus that causes cervical cancer.	HPV
Virus that causes nasopharyngeal carcinoma.	EBV
Virus that causes hepatocellular carcinoma.	HBV
What type of genes are affected by oncogenic viruses?	tumor suppressor genes
Review EBV and Burkitt's lymphoma.
Name the most important RNA oncogenic virus.	HTLV-1
How does HTLV-1 cause tumor formation?	Tax causes instability and mutation in host cell genes leading to T-cell proliferation
What bacteria is associated with B-cell lymphoma in MALT?	H. pylori
List 4 classes of genes affected by carcinogens.	oncogenes tumor suppressor genes apoptosis regulating genes mutator (caretaker) genes
Normal genes that play key roles in controlling cell proliferation and differentiation.	proto-oncogenes
Deregulated or altered proto-oncogenes that lead to development of cancer.	oncogenes
List 3 changes in gene structure that can cause activation of oncogenes.	point mutation translocation amplification
What is the most common point mutation in human cancers?	RAS mutation
Name the 2 chromosomes involved in translocation for chronic myelogenous leukemia.	9, 22
What enzyme activity is increased in chronic myelogenous leukemia?	tyrosine kinase
Amplification of which gene is involved in neuroblastoma?	N-MYC
Amplification of which gene is involved in breast cancer?	HER2
What type of proteins are encoded by oncogenes?	oncoproteins
List 5 classes of oncoproteins.	growth factors growth factor receptors signal transduction proteins nuclear (transcription) regulatory factors cyclin and cyclin-dependent kinases (cell cycle)
Review cell membrane diagram.
What is the most commonly mutated tumor suppressor gene?	p53
Name a tumor suppressor gene that acts on the cell cycle (G1-S).	retinoblastoma
How many alleles must be mutated to disrupt the function of tumor suppressor genes?	both (homozygous mutation)
Tumor suppressor gene associated with hereditary neurofibromatosis.	NF1
Tumor suppressor genes associated with breast carcinoma.	BRCA 1 & 2
Tumor suppressor gene associated with adenomatous polyposis cell carcinoma.	APC
Tumor suppressor gene associated with colon cancer.	DCC
Tumor suppressor gene associated with Wilm's tumor.	WT-1
What happens to telomeres with age?	telomeres shortened with age
Gene associated with colon and pancreatic cancers.	KRAS
Gene associated with B-cell lymphomas.	BCL2
Review multistep carcinogenesis.