CBCL 3 Flashcards
What are oncogenes and how are they formed?
oncogenes: genes involved in sustaining proliferative signaling
formed: GOF mutation. either change in structure of proto-oncogene (creating an abnormal gene product with aberrant function) or change in regulation of gene expression (aberrant expression or inappropriate production of normal protein)
what are the classes of oncoproteins?
- growth factors
- growth factor receptors
- proteins involved in signal transduction
- transcription factors/nuclear regulatory proteins
- cell cycle regulators (aka cyclins/CDK)
what are the tumor suppressor genes and how are they formed?
gatekeepers of the cell - prevent inappropriate cell division and growth
form: LOF mutation…either inactivation of both alleles or inactivation of protein function
how can both tumor suppressor alleles be inactivated?
- deletion of part or all of gene/chromosome
- gene mutation
- gene loss and reduplication of chromosome
- mitotic recombination
- methylation of promoter
what are the 3 most important tumor suppressor genes? how do they work?
- p53: on Chr 17; most common genetic defect in human neoplasms; upregulated by DNA damage, hypoxic stress and unregulated oncogene expression; accumulation of p53 leads to activation of genes involving DNA repair, cell cycle arrest at G1/S checkpoint, senescence, apoptosis; tumors are relatively resistant to chemo and radiation
- Rb: on Chr 13; normally inhibits transcription by binding TF E2F (most important checkpoint); E2F release allows G1-S phase transition; associated with inherited tumor called retinoblastoma (early in life: bilateral; late in life: unilateral)
- APC: normally binds and inhibits beta-catenin; prevents activation of transcription factors by beta-catenin; Familial adenomatous polyposis coli and sporadic colorectal cancer (and other neoplasms
How do growth factors work differently in cancer?
can be produced by cancer cells and set up an autocrine loop…works within tumors
What are three examples of growth factor receptors that are mutated in cancer?
- ERB-B2 = HER-2 in breast cancer: gene amplification…reacts to trastuzumab (monoclonal antibody)
- ERB-B1 = EGFR: lung cancer
- RET: multiple endocrine neoplasia and familial medullary thyroid carcinoma
what is a common mutation in many cancers that involve signal transduction proteins?
BRAF mutations -> type of RAS signal transduction
what is the mutant protein in chronic myelogenous leukeumia?
BCR/ABL translocation t(2,22) - can detect this by looking at the cell via FISH (color changes)
what are the two types of MYC and what cancers are they associated with?
- c-myc: t(8,14) in Burkitt lymphoma…MYC comes to be right in front of a promoter gene that is always active; get more of the normal gene product
- n-myc: overexpression in neuroblastoma due to gene amplification
what cyclin and CDK are associated with known cancers?
- cyclin D1: overexpression in mantle cell lymphoma
2. CDK4: amplification in melanoma and glioblastoma
what are the components of a tumor? define them.
Tumor parenchyma - consists of neoplastic cells within the tumor mass
Reactive stroma - non-neoplastic connective tissue, blood vessels, immune cells, etc. within the tumor mass
what is differentiation?
degree of resemblance (morphologic and biochemical) of neoplastic cells to the cell of origin
what is the difference between pleomorphism and anaplasia? what are they used for?
Pleomorphism - variation in size and shape
Anaplasia - lack of differentiation (highly atypical cells)
Used for grading of neoplasms - applied only to malignant neoplasms (which have more pleomorphism and anaplasia)
what is invasion?
growth of neoplastic cells beyond the site of origin (ex: epithelial neoplasms…growth beyond basement membrane)
