Neoplasia 4 Flashcards
____________ cancer is seen in chimney sweepers
Scrotal
Indirect acting carcinogen
Requires activation by P450
Aromatic amines and azodyes are chemical carcinogens linked to which carcinomas
Hepatocellular CA and bladder CA
Direct alkylating agents are carcinogens linked to what condition?
Leukemia
Mechanism of UV radiation causing damage to the body
- direct DNA damage - formation of pyrimidine dimers - nucleotide excision repair mechanism may be overwhelmed
Therapeutic ionizing radiation is associated with ____________ carcinoma
Thyroid carcinoma
carcinomas associated with EBV
Burkitt’s lymphoma and Nasopharyngeal carcinoma
Mechanisms of how HPV causes carinogenesis
HPV binds to p53 and other tumor suppressor genes and inactivated them → cell proliferation
__________ causes mutation int he cell (Mechanism of action of chemical carcinogens)
Initiator
Promoter causes ________________ (Mechanism of chemical carcinogens)
Clonal expansion
Mechanism of how EBV leads to Burkitt’s Lymphoma
Polyclonal proliferation → acquired translocation → c-myc activation → monoclonal proliferation
HTLV-1 is an RNA oncogenic retrovirus that is associated with ________________ (condition)
Human T cell leukemia/lymphoma
HTLV-1 proliferation is initially ______ and then becomes _______
Polyclonal; monoclonal leukemia
___________ protein stimulates proliferation, enhances cell survival and interferes with cell cycle controls in HTLV-1
Viral tax
HHV 8 is associated with condition?
Kaposi’s sarcoma
Where can driver mutations be found in the genome
They tend to be tightly clustered within cancer genes Direct contributors to the development org progression of cancer
where can passenger mutations be found in the genome
They are acquired mutations that DO NOT affect cellular behavior and occur at random spots throughout the genome
What classes of genes are affected by carcinogenesis?
- oncogenes (KRAS) - tumor suppressor genes (TP53) - apoptosis regulation genes (BCL2) - mutator (caretaker) genes (DNA mismatch repair) MSH2, MLH 1 - epigenetic changes such as DNA and histone methylation, acetylation, miRNA alteration and IncRNA changes
What kind of genetic change leads to retinoblastoma?
Deletion of 13q14
What kind of mutation causes neuroblastoma?
N-MYC amplification
How can a proto-oncogene transform into an oncogene
Point mutation, translocation, application or can affect the regulation of gene expression
most common point mutations that lead to carcinogenesis
RAS (oncogene) P53 (tumor suppressor)
Transloctions that can lead to over expression of oncogenes
T(9,22) = CML that activates BCR-ABL causing ↑ tyrosine kinase activity T(8,14) = burkitt’s lymphoma causing increased MYC protein production
Examples of gene amplifications that are carcinogenic
N-MYC = neuroblastoma HER2 = breast carcinoma
Oncoproteins are devoid of _____________ elements and they may act at different levels of signal transduction
Regulatory
How does proteins convenes become oncogenes
Retroviral transduction C onc ( by influences altering behavior in situ ) V onc (viral con gone similar to cellular protocol oncogenes
PDGF is a growth factor that can get mutated and become oncogenic and lead to _________
Astrocytoma
Epidermal growth factor receptor (ERBB2 (her2/neu) ) amplification (oncoprotein) can lead to ______ or _______
Breast carcinoma; stomach carcinoma
_______ of function mutation in a proto oncogene produces an oncogene which then produces oncoproteins
Gain
Mutated Rb gene _________ E2F causing ______
Releases; E2F is important for the G1-S transition) Proliferation (Retinoblastoma) Normally Rb is hyperphosphrylated and inhibits E2F
P53 upregulates _____ which disrupts _______
BAX; BCL2 Lung, colon, breast and ovary CA
Overexpression of BCL2 is linked to __________
CLL and other B cell lymphomas
