Lecture 15 3/18/24 Flashcards
What are the components of a morphologic diagnosis for neoplasm?
-tissue
-tumor type
-whether it is metastatic
What are the characteristics of the G1/S checkpoint?
-monitors DNA integrity
-irreversibly commits cell resources to DNA replication
-cell replication occurs independent to extracellular growth signals after this point
What are the characteristics of the G2/M checkpoint?
-pre-mitotic checkpoint
-ensures that DNA replication is accurate before cell divides
Which checkpoint is most important for carcinogenesis?
G1/S checkpoint
What are the possible cell types, based on division?
-continuously dividing
-non-dividing
-quiescent/can be induced to divide
What is the purpose of p53?
to stop cell division in cells with DNA damage and trigger either DNA repair or cell death
Which irreversible DNA mutations can lead to cancer development?
-proto-oncogenes
-tumor suppressor genes
-DNA repair genes
-genes regulating apoptosis
What are proto-oncogenes?
genes that promote autonomous cell growth
What happens when proto-oncogenes are mutated?
-growth factors are over-produced
-growth factor receptors are always “on”
-cyclins are over-produced, allowing progression through cell cycle
How many copies of a proto-oncogene must mutate to cause neoplasm?
one
What are tumor suppressor genes?
genes that stop the cell cycle
How many copies of a tumor suppressor gene must mutate to cause neoplasm?
two (both copies)
What are the characteristics of familial cancer syndromes?
-mutated tumor suppressor gene is passed on to offspring
-only one additional mutation required to inactivate the gene
-cancer often occurs earlier in life
What happens when DNA repair genes are mutated?
allows for the accumulation of more and more mutations in the cell genetics
What happens when genes that regulate apoptosis are mutated?
cells with DNA damage are allowed to continue living
What are the characteristics of multi-stage carcinogenesis?
-results from accumulation of mutations in a stepwise fashion over time
-nonlethal genetic damage is key
-tumor is formed by clonal expansion of a single precursor cell with genetic damage
What are the characteristics of multi-stage carcinogenesis initiation?
-mutation of single gene
-irreversible
What are the characteristics of multi-stage carcinogenesis promotion?
-proliferation of initiated cell in response to stimuli
-non-mutagenic
-reversible
-creates a proliferative environment
What are the characteristics of multi-stage carcinogenesis progression?
-progression from benign to malignant
-accumulation of mutations and uncontrolled cell growth
-irreversible
Which intrinsic factors can cause mutation?
-inherited
-mistakes
-reactive oxygen intermediates
Which extrinsic factors can cause mutation?
-viruses
-chemical carcinogens
-radiation
What are complete carcinogens?
carcinogens that can independently push a cell through initiation, promotion, and progression
What is grading?
-histologic diagnosis that assesses degree of differentiation, number of mitoses, and architectural features
-links histologic/microscopic features with clinical aggressiveness
What is staging?
-clinical diagnosis that assesses tumor size, degree of local invasion, lymph node involvement, and presence of distant metastases
-conveys extent of disease/neoplasia within the patient
