Neoplasia - 4 Flashcards
Examples of tumors with frequent p53 mutations (2)
What does this allow them to be resistant to
Examples: lung and colorectal cancers
Allows resistance to irradiation and chemotherapy
Germline mutations at 5q21 are associated with what disease?
APC (5q21)
Familial adenomatous polyposis
Germline mutation at 3p are associated with what disease?
VHL (3p)
VHL - hereditary renal cell cancers, pheochromocytomas, hemangioblastomas of the central nervous system, retinal angiomas, and renal cysts
What kind of complex is VHL protein a part of?
What is the critical substrate involved in this complex?
VHL is part of a ubiquitin ligase complex
Critical substrate: HIF1α (hypoxia-inducible transcription factor 1α)
In a hypoxic environment HIF1α translocates to the nucleus and turns on genes for which growth factors?
VEGF and PDGF
Mutation of 11p13 are associated with what disease?
Wilm’s tumor
WT1 protein is a transcriptional activator of genes involved with what?
renal and gonadal differentiation.
BCL2 gene family is located on what chromosome?
What is the function of the gene products produced?
Chromosome 18
Function: prevent mitochondrial (mt) leakage of cytochrome c
t(14;18) in B cells results in what action?
What disease is this associated with?
Results in overexpression BCL2 protein product
Associated with follicular lymphoma
In 85% - 95% of tumors there is upregulation of what enzyme?
What does this result in?
Telomerase
Limitless Replicative Potential
Describe tumor vasculature
The vessels are leaky and dilated, and have a haphazard pattern of connection
Tumors remain in a stage of vascular quiescence (small or in situ) for years until what event occurs?
What is the molecular basis for this event?
Angiogenic switch
Molecular basis: involves increased production of angiogenic factors and/or loss of angiogenic inhibitors
What two phases is the metastatic cascade divided into?
invasion of the extracellular matrix (ECM)
vascular dissemination, homing of tumor cells, and colonization.
Steps involved in the first phase of metastatic cascade?
Changes (“loosening up”) of tumor cell-cell interactions
Degradation of ECM
Attachment to novel ECM components
Migration of tumor cells
When does genomic instability occur?
What are 3 types of DNA-repair systems?
when both copies of the DNA repair gene are lost DNA repair systems: mismatch repair nucleotide excision repair recombination repair
HNPCC/Lynch Syndrome:
a. affect what anatomical location predominantly
b. results from defects in genes involved with which kind of DNA repair system?
c. Hallmark
d. genes involved in pathogenesis
a. familial carcinomas of the colon affecting predominantly the cecum and proximal colon
b. DNA mismatch repair
c. microsatellite instability
d. MSH2 , MLH1
Xeroderma pigmentosum:
a. results from defects in genes involved with which kind of DNA repair system?
b. Puts you at increased risk at an early age for what cancers?
c. cross linking of what prevents normal DNA replication in this disease?; what is the inciting stimulus?
a. nucleotide excision repair system.
b. skin cancers (basal cell carcinoma, squamous cell carcinoma, and malignant melanoma
c. cross linking of pyrimidine residues; UV radiation
List diseases with defects in DNA repair by Homologous Recombination (3)
What is their common mode of inheritance?
Diseases: Fanconi anemia Ataxia telangectasia Bloom syndrome Autosomal recessive
Hypersensitivity to DNA cross linking agents is seen in associated with what disease?
What does this put you at an increased risk of?
Fanconi anemia
developing malignant lymphomas, squamous cell carcinoma, and hepatocellular carcinomas; assoc with bone marrow aplasia
a. Mutation in gene ATM is associated with what disease?
b. What role does this gene usually play?
c. What does this mutation predispose people to?
a. Ataxia Telangectasia
b. important in recognizing and responding to DNA damage caused by ionizing radiation
c. malignant lymphomas and exhibit neural defects
Bloom syndrome:
a. what does the defective gene encode for?
b. what process does this defective gene product participate in (in terms of ionizing radiation)?
c. What does this mutation predispose people to?
a. A Helicase
b. participates in DNA repair by homologous recombination; – hypersensitivity to ionizing radiation
c. cancers such as gastrointestinal tumors and malignant lymphomas, developmental defects
a. what is the “eighth hallmark of cancer”?
b. explain this mechanism
c. what imaging technique would be used to visualize this?; what is being visualized?
a. Warburg effect
b. Even in the presence of ample oxygen, cancer cells shift their glucose metabolism away from the oxygen hungry, but efficient, mitochondria to glycolysis
c. PET scan; “glucose hunger” –> most tumors are PET positive but rapidly growing ones are markedly so
Translocation (9,22)
Chronic myelogenous leukemia (CML)
Translocation (8,21), (15,17)
Acute myeloid leukemia (AML)
