Cancer Genetics 1 Flashcards
What is cancer?
A group of disorders as a result of accumulation of somatic mutations; genetic diseases
What are the characteristics/hallmarks of cancers?
- uncontrolled cell division (unregulated cell proliferation)
- self sufficient in growth signals
- defective DNA repair
- immortal (evade apoptosis)
- capacity to invade surrounding tissues (metastasis)
- induce angiogenesis
What are the emerging hallmarks of cancer?
- avoiding immune destruction
- Deregulating cellular energetics
What are the enabling characteristics of cancer?
- Tumor-promoting inflammation
2. Genome instability and mutation
Explain cancer as a process
Cancer is a multi step process that requires multiple mutations
- Age related incidence of cancer develops from accumulation of several mutagenic events in single
- cancer results from mutated gene products or abnormally expressed genes
- mutations affect multiple cellular functions
- Incidence of most cancers rises exponentially with age
- Independent and random mutations are necessary for cell to become malignant
Outline the pathway for colon cancer?
- Normal colon epithelium + APC (patient between 30-50 years)
- Small adenoma +Kras (patient between 40-60 years)
- Large adenoma +PI3K Cell cycle/apoptosis genes TGF-B (patient 50-70 years)
- Carcinoma
Comeback to karyotypes
Come back to karyotypes
Describe the clonal origin of cancer cells
Clonal origin
-All cancer cells in primary and secondary tumors are clinical
- Clonal: Originated from a common ancestral cell that accumulated numerous mutations
- Supporting evidence : reciprocal translocations and X-inactivation demonstrate that cancer cells are clonal
Explain cancer stem cell hypothesis
Most cells within tumors do not proliferate
Cancer stem cell hypothesis
- tumor cells give rise to cancer stem cells that have capacity for self-renewal
- Stem cells: undifferentiated cells with capacity for self renewal
- Presence of cancer stem cells (CSCs) explains self-renewal capacity of a tumor
-CSCs divide asymmetrically to form new CSCs and progenitor (dark blue) cells that in turn give rise to differentiated cancer cells (light blue) that form bulk of the tumor
What is the role of reciprocal translocations play in cancer?
Reciprocal translocations are characteristic of many cancers
- include white blood cell cancers such as leukemia’s and lymphomas
- Example: chronic myeloid leukemia: reciprocal translocation between chromosome 9 and 22
- translocation is present in all tumor cells
What is the role of X-inactivation in cancer development?
X-chromosome inactivation occurs early in development at rando:
-All cancer cells within a tumor, both primary and metastatic, within one female individual contain the same inactivated X-inactivated chromosome
Cancer can result from…
- increased cell division
- decreased rates of cell death(evasion of apoptosis)
What happens to cancer cells in interphase?
Interphase-interval between mitotic division
-Cell grows (G1 and G2 phases) and replicates it’s DNA (S phase)
- Cells that stop proliferating enter G0
- Do not grow or divide but are metabolically active(neurons)
-Cancer cells are unable to enter G0 and cycle continuously
What are the cell cycle control and checkpoints?
- G1/S, G2/M and M checkpoints
- 3 distinct checkpoints where the cell monitors external signals and internal equilibrium
- Cells decide whether to proceed to the next stage of the cell cycle
What is the function of the G1/S as a cell cycle checkpoint?
Cell monitors size and DNA integrity
What is the function about the G2/M cell cycle checkpoint?
Cell monitors DNA synthesis and damage