Chapter 3 Flashcards
What is Neoplasia?
new tissue growth, that is unregulated, irreversible and monoclonal
Which enzyme can be used to determine clonality
Glucose-6-phosphate dehydrogenase . Multiple Isoforms of G6PD exist; only one isotype is inherited from each parent
In females , one isoform is randomly inactivated in each cell by lyonization (G6PD is present on the X chromosome)
Normal ratio of active isoforms in cells in any tissue is 1:1
1:1 ratio is maintained in hyperplasia but not in neoplasia since neoplasia is monoclonal .
Clonality can also be determined by androgen receptor isoforms, which are also present on X chromosome
How is the clonality of B lymphocytes determined
Clonality of B lymphocytes is determined by Immunoglobulin (Ig) light chain phenotype
Each B cell exhibits light chains that are either kappa or lambda
Normal Kappa to Lambda ratio is 3:1
This ratio is maintained in hyperplasia but not in neoplasia
Benign Tumor cells arising from the Epithelium, Mesenchyme, Lymphocyte,
Melanocyte are called?
Epithelium - Adenoma, Papilloma
Mesenchyme - Lipoma
Lymphocyte- (does not exist)
Melanocyte-Nevus
Malignant Tumor cells arising arise from the epithelium, mesenchyme,lymphocyte and melanocyte are called?
Epithelium- Adenocarcinoa, Papillary carcinoma
Mesenchyme- Liposarcoma
Lymphocyte -Lymphoma/Leukemia
Melanocyte-Melanoma
What is the leading cause of death in adults
Cardiovascular disease
cancer is 2nd (prostate/breast most common by incidence followed by lung then colorectal, by mortality Lung cancer is first followed by breast/prostate and then colorectal) followed by cerebrovascular disease
What is the leading cause of death in children
Accidents
Cancer is 2nd and congenital defects is third
What is the function of proto-oncogenes?
essential for cell growth and differentiation;mutations of proto-oncogenes form oncgenes that lead to unregulated cell growth.
What are the categories of oncogenes
Growth Factors (Induce cellular growth)
Growth Factor Receptors(mediate signals from growth factors)
Signal Transducers(relay receptor activation to the nucleus)
Cell cycle regulators
What are the categories of oncogenes
Growth Factors (Induce cellular growth)
Growth Factor Receptors(mediate signals from growth factors)
Signal Transducers(relay receptor activation to the nucleus)
What are five cancer causing chemicals and their associated cancers ?
Aflatoxins (derived from aspergillus, contaminant of stored grains) -Hepatocellular carcinoma
Alkylating agents (Side effect of chemotherapy) - Leukemia/Lymphoma
Alcohol - Upper esophagus, Squamous cell carcinoma of the oropharynx, Pancreatic cancer, Hepatocellular carcinoma, present in cigarette smoke) - Squamous cell carcinoma of skin,lung cancer, angiosarcoma of liver
Asbestos Lung cancer and mesothelioma (less likely)
Cigarette smoke : Carcinoma of the oropharynx , esophagus,lung, kidney and bladder
Nitrosamines (In smoked foods, responsible for the high rate of stomach cancer in japan)-stomach cancer
Napthylamine (derived from cigarette smoke)- Urothelial carcinoma of bladder
Vinyl Chloride (Occupational exposure ; used in the manufacturing of Polyvinyl chloride (PVC) in pipes)
Nickel, Chromium,Berrylium,Silica (occupational exposure)- Lung cancer
What are 5 oncogenic viruses
EBV-Nasopharyngeal Carcinoma,Burkitt Lymphoma
HHV-8 - kaposi sarcoma
HBV and HCV - Hepatocdllular carcinoma
HTLV-1 -Adult Tcell leukemia/lymphoma
High risk HPV(subtypyes 16,18,31,33) Squamous cell carcinoma of vulva, vagina,anus and cervix,; adenocarcinoma of cervix.
What are the two cancer causing radiation and their associated cancers
Ionizing (reactor accidents and radiation therapy) (Generates free radicals)- AML , CML and papillary carcinoma of the thyroid
Non Ionizing (UVB sunlight is the mos common cause- results in the formation of pyrimidine dimers in DNA, which are normally excised by restriction endonucleases) - Basal cell cacinoma,squamous cell carcinoma and melanoma of the skin.
What is the function of Tumor suppressor genes
Regulate cell growth and hence decrease the risk of tumor formation
example: P53 and Rb (retinoblatoma) , P53 reguulates progression of the cell cycle from G1 to S phase
1. In response to DNA damage, P53 slows the cell cycle and upregulates DNA repair enzymes .
2.If DNA repair is not possible , p53 induces apoptosis
i. p53 regulates BAX, which disrupts Bc12.
ii. Cytochrome c leaks from the mitochondria activating apoptosis.
3. Both copies of the p53 gene must be knocked out for tumor formation (Knudson two-hit hypothesis)
i. Loss is seen in >50% of cancers
ii. Germline mutation results in Li-Fraumeni Syndrome (2nd hit is somatic) characterized by propensity to develop multiple types of carcinomas and sarcomas
How does Rb funtion as a tumor suppressor gene?
Rb “holds” the E2F transcription factor, which is necessary for the transition to the S phase
E2F is released when Rb is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex
Rb mutation results in constitutively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells
Both copies of Rb gene must be knocked out for tumor formation (Knudson two hit hypothesis )
