Ch. 20 Flashcards
Oncogenes
cancer when overexpressed or constitutively activated and dominant effects of mutations
Tumor Suppressor Genes
causes cancer when they are deleted or inactivated, recessive effects of mutations and loss of function (Wilms’ Tumor)
DNA repair genes
allows other mutations to persist, inherited dna repair disorders (single-gene) and rare
cause diverse and widespread tumors
Proto-oncogenes
genes that promote cell division BUT expression at the wrong time of development or place in body leads to oncogenes
What is the activation of oncogenes associated with?
point mutation, chromosomal translocation, inversion
causes gain of function that is dominant
What happens when a virus infects a cell?
inserts its dna next to proto-oncogene, viral dna and oncogene transcribed, changes from encoded protein trigger mitosis to cancer
How does p53 affect cancer?
p53 is a transcription factor that determines if cell repair dna replication errors or dies by apoptosis and is genetic mediator between environmental insults and cancer development (somatic mutation)
Li-Fraumeni Syndrome
Germline Mutations
Cancer susceptibility passed onto offspring, cancer develops when second somatic mutation occurs, mutation every cell
Somati Mutations
sporadic in non-sex cells, single dominant mutation or two recessive mutations, susceptibility not passed to offspring
Dedifferentiated Cancer Cells
less specialized than normal cell types
Characteristics of Cancer Cells
- looks different
cell surface has different types and/or # of antigens - heritable mutations
- transplantable
- dedifferentiated
- invasiveness
- metastasize (move to new location)
- induce angiogenesis (formation of new capillary extensions)
- vascular endothelial growth factor (VEGF)
- secrete hormones that encourage own growth
- aneuploid: miss/have extra chromosomes
How can cancers begin at the cellular level?
activation of stem cells that produce cancer cells, dedifferentiation, increase in proportion of a tissue that consists of stem cells or progenitor cells, faulty tissue repair
How can a cancer cell descend?
from stem cell that yields differentiated daughter cells that retain capacity to self-renew OR specialized cell that loses some of its features and can divide
Cancer stem cells
produce both cancer cells and abnormal specialized cells (in brain, blood, epithelium cancers)
How does cancer begin by loss of specialization?
cells lose distinguishing characteristics as mutations occur during division or express “stemness” genes that override signals to remain specialized
How can cancers originate from tissues?
loss of balance at tissues in favor of cells that can divide continually or frequently. tumor forms from extra stem and progenitor cells from balance shift
Driver mutation
Provides the selective growth advantage to a cell that defines cancerous state (oncogenes or tumor suppressor genes generated, 2% genes involved in cell cycle or DNA repair) `
Passenger Mutation
occurs in cancer cell (or noncancerous), does not cause or propel cancer’s growth/spread, thousands of genes can harbour mutations
What are the “Three Strikes” of Cancer?
breakthrough, expansion, invasion
Breakthrough
First driver mutation; cancer begins in single cell when oncogene is turned on or tumor suppressor gene is turned off, lifting controls on cell division
Expansion
Second driver mutation; cancer cell divides more and can survive in environment w scarce resources
Invasion
Further mutations in multiple pathways; cancerous tumor grows and spreads locally then attracts blood vessels and enters
Diagnosing Cancer- Liquid Biopsy
checking cell-free tumor DNA (ctDNA) in blood plasma for oncogene/tumor suppressor mutations
What are the advantages of liquid biopsy?
asymptomatic tumors can be detected early, better specificity than protein biomarkers, monitor tumor recurrence after treatment
what is the disadvantage of liquid biopsies?
false positive findings
