The document discusses how cancer evolves within the human body through a process of mutation, natural selection, and clonal expansion similar to biological evolution. Cancer cells accumulate mutations that allow them to grow and survive faster than normal cells over many generations, just as species accumulate adaptations over generations. This evolutionary process allows cancer to become more aggressive and develop resistance to therapies. The document uses examples like Tasmanian devils, dogs, and HeLa cells to illustrate how cancer can even transfer between individuals like a contagious disease.

1. The Devil’s Tumor
June 14, 2013
Carl Zimmer
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2. Disclosures
• I
have
no
conflicts
of
interest
to
disclose
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3. Causes of death in the United States, 2010
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6208a8.htm?s_cid=mm6208a8_w, http://who.int
Worldwide, 7.8 million deaths from cancer each year
(A San Francisco every month)
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4. Rick Eh/Flicker via Creative Commons http://www.flickr.com/photos/rick-in-rio
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8. George von Dassow, University of Oregon http://www.cell.com/cell_picture_show-cellcycle
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9. x
Mutations that speed up growth
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10. x
x
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Mutations that speed up growth
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11. x
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Mutations that speed up growth
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12. x
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Mutations that speed up growth
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13. Prostate
cancer
cells
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14. Cancer Evolves
Charles Darwin
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15. Based on Gregory, Evo Edu Outreach (2009) 2:156–175
Natural Selection
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16. Generation 1
Based on Gregory, Evo Edu Outreach (2009) 2:156–175
Natural Selection
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17. Generation 1
Based on Gregory, Evo Edu Outreach (2009) 2:156–175
X
X
Non-random
survival
X
X
Natural Selection
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18. Generation 1
Reproduction and mutation
Generation 2
Based on Gregory, Evo Edu Outreach (2009) 2:156–175
X
X
Non-random
survival
X
X
Natural Selection
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19. Generation 1
Reproduction and mutation
Generation 2
Based on Gregory, Evo Edu Outreach (2009) 2:156–175
X
X
Non-random
survival
X
X
Non-random
survival XXX
X
Natural Selection
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20. Generation 1
Reproduction and mutation
Generation 2
Based on Gregory, Evo Edu Outreach (2009) 2:156–175
X
X
Non-random
survival
X
X
Generation 3
Reproduction
and mutation
Non-random
survival XXX
X
Natural Selection
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21. Generation 1
Reproduction and mutation
Generation 2
Based on Gregory, Evo Edu Outreach (2009) 2:156–175
Many generations of
mutation and natural
selection
Generation X
X
X
Non-random
survival
X
X
Generation 3
Reproduction
and mutation
Non-random
survival XXX
X
Natural Selection
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22. Friday, June 14, 13

23. Ding, Li, et al. Nature 2012 481: 506-510
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24. Therapy Relapse
resistant
sub-clone
Aktipis & Nesse, 2013
Evolution:Why Chemotherapy Fails
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25. J. Baylor Roberts/National Geographic
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27. http://en.wikipedia.org/wiki/Humphrey_Bogart
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28. img.photobucket.com/albums/v382/Matthoggua/Dimfuture/jackalope-1.jpg
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29. kuleuven.be/rega/mvr/research.html
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30. Papillomavirus
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31. Friday, June 14, 13

32. HeLa cells
Landry, Jonathan JM, et al. G3: Genes| Genomes| Genetics (2013)
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33. LeighVanValen
Van Valen LM, Maiorana VC 1991.
Hela, a new microbial species.
Evol. Theory 10: 71-74.
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34. HeLa cells
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35. Helacyton gartleri?
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36. Lactobacillus bulgaricus
van de Guchte et al, PNAS 2006 103:9274-9
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37. Glassy-winged sharpshooter (with residents)
Nancy Moran PNAS 2007 (104) Suppl 1 8627-8633
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38. http://www.tassiedevil.com.au
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39. en.wikipedia.org/wiki/File:Taz-Looney_Tunes.svg
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40. Courtesy Kathy Belov
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41. tassiedevil.com.au
Devil’s Facial Tumor Disease
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42. Friday, June 14, 13

43. Friday, June 14, 13

44. WhatYou’d Expect From
Normal Cancer...
Host DNA Tumor DNA
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45. WhatYou’d Expect From
Normal Cancer...
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48. Friday, June 14, 13

49. Murchison et al. Cell 2012 148: 780-791
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50. Tony Pappenfuss
Walter & Eliza Hall Institute
of Medical Research
Melbourne,Australia
Murchison et al Science. 2010 327:84-7
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51. www.tassiedevil.com.au
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52. Image: en.wikipedia.org/wiki/File:MHC_expression.svg
See: Siddle et al, PNAS 2013 110:5103-8
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53. flickr.com/photos/australianshepherds/3212875937/
K. Belov, Bioessays. 2012 34:285-92, Rebbeck et al, Science. 2011 331:303
Canine TransmissibleVenereal Tumor
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56. Maria Island
Paul Benjamin, Flickr, Creative Commons http://www.flickr.com/photos/paul_benjamin
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57. Friday, June 14, 13

58. Ali and Lear, Journal of Skin Cancer 2012 doi:10.1155/2012/404615
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61. Friday, June 14, 13

62. See Magee et al, Cancer Cell 2012 3:283, & I. O'Neill Stem Cells 2011 29:1909-1914
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63. See Magee et al, Cancer Cell 2012 3:283, & I. O'Neill Stem Cells 2011 29:1909-1914
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64. X
X
See Magee et al, Cancer Cell 2012 3:283, & I. O'Neill Stem Cells 2011 29:1909-1914
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65. X
X X
X
See Magee et al, Cancer Cell 2012 3:283, & I. O'Neill Stem Cells 2011 29:1909-1914
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66. Gilbertson and Graham, Nature 2012 488, 462–463
Curing Cancer:All Cancer Cells Are Not Equal
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69. Thanks to Carlo Maley, Athena Aktipis,
Rebecca Skloot, Beata Ujvari, and Kathy Belov
For more information, please visit
carlzimmer.com
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70. Friday, June 14, 13

71. Opportunity for Somatic Evolution in a Human Lifetime
• Mutation rate:
• Point mutations: 10-11 – 10-7 bp/cell generation
• Chromosomal abnormalities: 10-6 per cell generation
• Methylation changes: ~10-3 per CpG/cell generation
• Number of mutations detected: 101 – 105
• Generation time: 1 – 3 days
• Time from initiation to malignancy: decades (3 – 60 years)
• Number of generations: 102 – 104
• Population size: 109 – 1012 cells
• Rate of clonal expansions: unknown
More potential for evolution than the history of H. sapiens
Note: uncertainty about all these parameters
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