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42 Cards in this Set

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What is the genetic related explanation for breast and ovarian tumors?
BRCA1, BRCA2 gene mutations
What is the genetic related explanation for multiple endocrine neoplasia 1 & 2?
MEN1, RET gene mutations
What is the genetic related explanation for hereditary nonpolyposis colon cancer?
MSH2, MLH1, MSH6 gene mutations
What is the genetic related explanation for nevoid basal cell carcinoma syndrome?
PATCH gene mutation
What are four examples of chronic inflammation that can lead to cancer?
1. ulcerative colitis -> colorectal CA
2. viral hepatitis -> hepatocellular CA
3. helicobacter pylori -> gastic CA, MALT lymphoma
4. Chron's disease -> colorectal CA
What precancerous conditions can lead to cancer?
1. cervical dysplasia (HPV) -> cervical carcinoma
2. actinic keratosis -> squamous cell CA
3. chronic atrophic gastritis/pernicious anemia -> castric CA
4. oral/penile, vulvar leukoplakia -> squamous cell CA
5. colonic adenoma -> colon CA

most of the time this is nonmalignant, though
What are the four classes of regulatory genes that provide the molecular basis of cancer?
1. protooncogenes
2. tumor suppressor genes
3. genes that regulate apoptosis
4. genes involved in DNA repair
What are cyclins roles in the cell cycle?
During the cell cycle (first in mid G1) cyclins are released and bind cyclin dependent kinases (CDKs) that phosphorylate target proteins required to continue the cell cycle. This provides an on/off switch for the cell cycle.
What are genomic instability syndromes?
congenital defects in DNA repair genes which can lead to cancer
What are microsatellites and how do they relate to DNA repair and cancer?
microsatellites are tandem repeats of one to six nucleotides that reside in every tissue and can expand and contract and produce errors in mismatch repair. this is called microsattelite instability
What causes HNPCC (hereditary nonpolyposis colon cancer)?
germline mutations in DNA mismatch repair genes MSH2, MLH1, PMS, PMS2
What is nucleotide excision repair?
DNA repair by excision of mutations caused by any number of agents including UV light. the NER pathway takes care of this (nucleotide excision repair pathway)
What condition involves an autosomal recessive NER mutation?
Xeroderma pigmentosum
"Children of the Night"
What is the cause of ataxia-telangiectasia?
autosomal mutation of ATM gene resulting in absence of loss of function. this function is important because it codes for a protein kinase that senses dsDNA breaks and phosphorylates p53, which stops the cell cycle.
What is bloom syndrome?
autosomal recessive defect in gene on chromosome 15 which encodes BLM helicase
What is fanconi anemia?
autosomal recessive defect in several genes that causes dysfunctional DNA repair mechanisms
What gene mutations inhibit proper DNA repair mechanisms and lead to breast and ovarian cancers?
BRCA-1 and BRCA-2 genes
What four examples of cancer cells that produce growth factors to self-promote?
1. PDGF-B -> SIS protooncogene -> astrocytoma, osteosarcoma
2. fibroblast growth factors -> HST-1, INT-2 protooncogenes -> stomach, bladder, breast CA; melanoma
3. TGF-alpha -> TFG alpha protooncogene -> astrocytomas, hepatocellular CA
4. Hepatocyte Growth Factor -> HGF protooncoogene -> Thyroid CA
What is erbitux and what is the significance?
Erbitux is an antibody which acts as an epidermal growth factor receptor (EGFR) inhibitor, given by intravenous infusion for treatment of metastatic colorectal cancer and head and neck cancer.
What is the pathogenesis of common conditions caused by problems with self-production of growth signal nuclear regulatory proteins in CA?
transcriptional activators -> C-MYC, N-MYC, L-MYC protooncogenes -> Burkitt lymphoma (C-MYC), neuroblastoma (N-MYC), small cell lung CA (N-MYC, L-MYC)
What are two examples of self-production of growth signals that are cell cycle regulators?
1. cyclins -> cyclin D, cyclin E -> mantle cell lymphoma (D translocation), breast & esophageal CA (D amplification), breast CA (E amplification)
2. cyclin dependent kinase -> CDK4 protooncogene -> glioblastoma, melanoma, sarcoma
What causes both Burkitt lymphoma and CML (chronic myelogenous leukemia)?
chromosomal swap where myc oncogene (burkitt) and abl oncogene (CML) self-promote due to a chromosomal aberration and -> CA
What nuclear regulatory protein proliferation is responsible for neuroblastoma?
N-MYC which produces double minutes and causes there to be an HSR (Homogeneously staining region) on the chromosome that is detectable. And HSR is found on chromosomes in the nucleus of neuroblastoma CA cells and is several repeating units of what encodes for N-MYC!
What are six tumor suppressor genes and what cancers result in their mutation?
1. RB -> retinoblastomas, osteocarcomas
2. p53 -> many CA
3. WT-1 -> Wilms tumor
4. p16 -> melanoma, pancreas/breast/esophagus CA
5. BRCA-1, BRCA-2 -> breast, ovarian CA
6. KLF6 -> prostate
Why does a mutation in p53 tumor suppressor gene cause problems that lead to CA?
p53 is involved in cell cycle arrest and initiation of apoptosis in response to DNA damage. no cell cycle arrest or apoptosis -> proliferation of damaged cells -> CA
Why does a mutation of the APC gene cause thousands of adenomatous colon polyps at an early age?
APC down regulates B-catenin which binds to transcription factor TCF -> upregulation of cell proliferation
What gene protects tumor cells from apoptosis?
BCL-2 gene which normally causes cell death, so these CAs are usually slow growing not because of enhanced proliferation but because of degradated apoptotic events
How can CA cells have limitless replicative potential?
usually telomers are degraded until there are so few that a cell must stop replicating, but germ cells, somatic cells, and CA cells get around it. telomerase is present in CA cells which adds telomers to CA cell chromosomes.
What is angiogenesis?
creation of new blood vessels
What do tumors do to allow themselves to increase to a size beyond what is required before angiogenesis?
tumors produce angiogenic factors that cause angiogenesis:
1. VEGF
2. FGF
What is the key feature of malignancy?
metastasis (2 main steps):
1. invasion of the extracellular matrix ECM
2. vascular dissemination of tumor cells
What is the Metastatic signature?
theory that many or all tumor cells have multiple abnormalities that when combined produce malignancy.
What are metastatic variants?
the intermediates between non-metastatic and metastatic tumors are referred to as metastatic variants. consider non-metastatic, metastatic variant/signature, metastasis as the three functional steps in becoming metastatic
What are the steps of ECM invasion for a metastasizing tumor?
1. detachment of tumor cells from each other
2. attachment of tumor cells to matrix
3. degradation of ECM
4. migration of tumor cells
What details occur during the ECM invasion step of detachment of tumor cells from each other?
E-cadherin facilitate adhesion in epithelial cells and tumor cells. in epithelial tumors, E-cadherin is downregulated or E-cadherin's receptor protein (catenin protein) is not viable because of a mutation in the catenin gene.
What details occur during the ECM invasion step of attachment of the tumor cells to the matrix?
tumor cells attach to the basement membrane circa laminin and fibronectin receptors attaching to integrins expressed by the tumor such as laminin, fibronectin, collagen, and virtonectin
What details occur during the ECM invasion step of degradation of the ECM?
serine, cysteine, and matrix metalloproteinases (MMPs) are responsible for degredation and are secreted by tumor cells. plasminogen activator secretion helps degrade the basement membrane. these cleavage products also have growth promoting, angiogenic, and chemotactic activities, AND Type IV collagen breakdown produces antiangiogenic endostatin and tumstatin
What details occur during the ECM invasion step of migration?
fibronectin and the autocrine motility factor play a role in movement through the basement membrane
What steps occur during the vascular dissemination of tumor cells?
1. in the blood stream tumor cells clump together with platelets
2. tumor cells seed in "good soil" muscle cells are not good soil, so rare metastasis
3. tumor cells express adhesion molecules at the site of seeding
What two chromosomal changes activate protooncogenes?
1. most commonly translocations
2. less commonly inversions
What is are 4 examples of translocation that causes CA?
1. Burkitt lymphoma where MYC on chromosome 8 is placed close to Ig heavy chain gene on chromosome 14 -> overexpression of MYC
2. mantle cell lymphoma where cyclin D1 gene -> near Ig heavy chain t(11;14) -> overexpression of cyclin D1
3. follicular lymphoma where bcl-2 gene -> near Ig heavy chain t(14;18) -> activation of bcl-2
4. philadelphia chromosome in chronic myeloid leukemia and acute lymphoblastic leukemia where c-ABL -> BCR region t(9;22) -> tyrosine kinase protein production
What is gene amplification in regard to CA?
overproduction of a gene, resulting in hundreds of copies of a protooncogene in a tumor cell which can sometime correlate with prognosis

ex. N-MYC in neuroblastomas
ERB B2 in breast cancer