slide set 21 Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

cancer cells are defined by:

A

reproduce without, or in defiance of, normal signals

invade and colonize areas reserved for other cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

non-cancerous somatic cells facts

A
  • cells need signals to survive
  • cells need signals to grow and divide
  • cells need to adhere to a surface or other cells (or other proteins)
  • damaged cells will activate apoptosis

cancer cells ignore all this!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how does a tumor begin

A

with one cell

microevolution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

carcinomas

A

cancer of epithelial cells

80% of cancers are epithelial in origin

this is because epithelial cells are more exposed to elements (more on the surface)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

sarcomas

A

connective or muscle cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

leukemias and lymphomas

A

blood cell cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

benign tumor

A

“oma” ex: adenoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

malignant

A

for epithelial, “carcinoma” EX: adenocarcinoma

for connective/muscle, “sarcoma” EX: chondrosarcoma

also over-profileration, but some cells escape basal lamina and can move beyond the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

tumor cell population

A

cancer starts with a single cell

  • but that cell reproduces and mutates as time passes
  • mutations within the growing population:
    • select for the fastest growing and least inclined to respond to signals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

clonal origin

A

cancer starts with a single cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

evidence for clonal origin

A
  • chronic myelogenous leukemia
  • begins with rare event that leads to forming of Philadelphia chromosome
    • all patients have a chromosome translocation between chromosomes 9 and 22 in all of the tumor cells
    • creates a novel enzyme
  • all patients with this type of cancer: every cell has the philadelphia chromosome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

because cancer arises from a single cell, changes must be heritable (2 explanations)

A
  1. Must be mutation to genes
    1. somatic mutations because they occur in somatic cells (cells of the body) not germ cells (cells that will form eggs or sperm)
  2. Epigenetic changes
    1. heritable changes in gene expression from chromatin structure
      1. heritable = passed down to daughter cells, not offspring
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

evidence that multiple mutations are required to turn a cell cancerous

A
  • cancer incidence rises with age
  • if a single mutation was sufficient and equally likely at any time, we would expect a linear rate of incidence
  • instead, cancer requires multiple mutations before all normal regulatory controls are lost
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

2 big summarizing features

A
  1. cancer develops from a single cell
  2. multiple mutations are required to transform a cell

these were confirmed by sequencing entire genomes of single cells within a tumor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

clonal evolution

A
  • accumulation of mutations over time: slow at first
  • tumor progression is an evolutionary process as new mutations increase cell proliferation
  • there are sub-clones within tumors
    • genetic diversity within a tumor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

cancer cells are genetically unstable

A
  • sequence mutations, chromosomes translocations, deletions, duplications, structure (heterochromatin)
  • mitotic chromosomes:
    • each chromosome should ONLY have one color
      • color marks the sequence typicaly of that chromosomes in a normal cell
17
Q

hallmark 1 of cancer

A

cancer cells display altered control of cell growth

most normal cells stop proliferating once they have carpeted the dish with a single layer of cells

proliferation is inhibited by contacts with other cells: contact inhibition

cancer cells disregard restraints and continue to grow and pile on one another

18
Q

hallmark 2 of cancer

A

cancer cells have altered sugar metabolism

A) cells that are not proliferating will normally oxidize nearly all of the glucose they import from blood to produce ATP through oxidative phosphorylation

cells only derive most energy from glycolysis when deprived of oxygen

B) Tumor cells produce abundant lactate even in presence of oxygen

bc of increased rate of glycolysis that is fed by a large increase in rate of glucose import

tumor cells resemble rapidly proliferating cells in embryos (and during tissue repair)

19
Q

tumor growth involves both:

A

increased cell division and decreased apoptosis contribute to growth

20
Q

cells still die within a tumor, just less death by apoptosis

A
21
Q

hallmark 3 of cancer

A

avoid replicative senescence

  • our somatic cells have limited capacity to replicated
    • 25-50 times for human fibroblasts
    • The length of the telomere at the ends of chromosomes shortens with each replication
  • cancer cells can re-express telomerase, which extends telomeres and prevents replicative senescence
22
Q

tumor cells in context

A

the microenvironment and local signals contribute to tumor growth and speed

communication among different cell types play a role in tumor development

23
Q

Recall: most cancers are of epithelial origin

A

cells must break cell-cell contacts and get through the basal lamina to spread

24
Q

metastasis

A

a multi-step process that few cells can survive

25
Q

mutations include:

A
  • change in chromosome copy number, intra and interchromosomal rearrangements
    • also point mutations
    • sequencing all protein coding regions:
      • ~50 genes are mutated in several cancers
26
Q

mutations

A

some mutations drive cancer progression. Others are passengers.

  • current best guess: ~300 genes are critial for cancer development and progression
  • need >1 driver mutation, maybe up to 10
27
Q

driver mutations are common throughout biology

A
28
Q

Driver mutations:

A

two broad types of cancer-critical mutations

oncogenes: gain of function mutations lead to cancer

tumor suppressor genes: loss of function mutations (recessive, both alleles of cancer-critical gene must be lost)

29
Q

~300 mutated proteins fall into a few key circuits and signal transduction pathways

A
30
Q

EXAMPLE: Glioblastoma

A
  • 91 patient tumors were sequenced
  • Mutations in 3 pathways stood out as commonly hit (~75%)
  • Broadly, these control:
    • cell growth
    • cell division
    • responses to stress and DNA damage