The Devil’s Tumor

June 14, 2013

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Carl Zimmer

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Disclosures

• I  have  no  conflicts  of  interest  to  disclose

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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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Rick Eh/Flicker via Creative Commons http://www.flickr.com/photos/rick-in-rio

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George von Dassow, University of Oregon http://www.cell.com/cell_picture_show-cellcycle

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Mutations that speed up growthFriday, June 14, 13

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Mutations that speed up growthFriday, June 14, 13

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Mutations that speed up growthFriday, June 14, 13

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Mutations that speed up growthFriday, June 14, 13

Prostate cancer cells

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Cancer Evolves

Charles Darwin

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Based on Gregory, Evo Edu Outreach (2009) 2:156–175

Natural Selection

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Generation 1

Based on Gregory, Evo Edu Outreach (2009) 2:156–175

Natural Selection

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Generation 1

Based on Gregory, Evo Edu Outreach (2009) 2:156–175

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Non-random survival

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Natural Selection

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Generation 1

Reproduction and mutation

Generation 2

Based on Gregory, Evo Edu Outreach (2009) 2:156–175

XX

Non-random survival

XX

Natural Selection

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Generation 1

Reproduction and mutation

Generation 2

Based on Gregory, Evo Edu Outreach (2009) 2:156–175

XX

Non-random survival

XX

Non-random survival XXX

XNatural Selection

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Generation 1

Reproduction and mutation

Generation 2

Based on Gregory, Evo Edu Outreach (2009) 2:156–175

XX

Non-random survival

XX

Generation 3

Reproduction and mutation

Non-random survival XXX

XNatural Selection

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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

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Non-random survival

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Generation 3

Reproduction and mutation

Non-random survival XXX

XNatural Selection

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Ding, Li, et al. Nature 2012 481: 506-510

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Therapy Relapse

resistantsub-clone

Aktipis & Nesse, 2013

Evolution: Why Chemotherapy Fails

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J. Baylor Roberts/National Geographic

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http://en.wikipedia.org/wiki/Humphrey_Bogart

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img.photobucket.com/albums/v382/Matthoggua/Dimfuture/jackalope-1.jpg

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kuleuven.be/rega/mvr/research.html

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Papillomavirus

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HeLa cells

Landry, Jonathan JM, et al. G3: Genes| Genomes| Genetics (2013)Friday, June 14, 13

Leigh Van ValenVan Valen LM, Maiorana VC 1991.

Hela, a new microbial species. Evol. Theory 10: 71-74.

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HeLa cells

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Helacyton gartleri?

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Lactobacillus bulgaricus

van de Guchte et al, PNAS 2006 103:9274-9

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Glassy-winged sharpshooter (with residents)

Nancy Moran PNAS 2007 (104) Suppl 1 8627-8633

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http://www.tassiedevil.com.au

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en.wikipedia.org/wiki/File:Taz-Looney_Tunes.svg

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Courtesy Kathy Belov

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tassiedevil.com.au

Devil’s Facial Tumor Disease

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Annual Reviews

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What You’d Expect From Normal Cancer...

Host DNA Tumor DNA

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What You’d Expect From Normal Cancer...

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Annual Reviews Friday, June 14, 13

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Murchison et al. Cell 2012 148: 780-791

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Tony Pappenfuss Walter & Eliza Hall Institute of Medical ResearchMelbourne, Australia

Murchison et al Science. 2010 327:84-7

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www.tassiedevil.com.au

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Image: en.wikipedia.org/wiki/File:MHC_expression.svg

See: Siddle et al, PNAS 2013 110:5103-8

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flickr.com/photos/australianshepherds/3212875937/

K. Belov, Bioessays. 2012 34:285-92, Rebbeck et al, Science. 2011 331:303

Canine Transmissible Venereal Tumor

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Maria Island

Paul Benjamin, Flickr, Creative Commons http://www.flickr.com/photos/paul_benjaminFriday, June 14, 13

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Ali and Lear, Journal of Skin Cancer 2012 doi:10.1155/2012/404615

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See Magee et al, Cancer Cell 2012 3:283, & I. O'Neill Stem Cells 2011 29:1909-1914

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See Magee et al, Cancer Cell 2012 3:283, & I. O'Neill Stem Cells 2011 29:1909-1914

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See Magee et al, Cancer Cell 2012 3:283, & I. O'Neill Stem Cells 2011 29:1909-1914

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See Magee et al, Cancer Cell 2012 3:283, & I. O'Neill Stem Cells 2011 29:1909-1914

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Gilbertson and Graham, Nature 2012 488, 462–463

Curing Cancer: All Cancer Cells Are Not Equal

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Thanks to Carlo Maley, Athena Aktipis, Rebecca Skloot, Beata Ujvari, and Kathy Belov

For more information, please visit carlzimmer.com

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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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