Renato Dulbecco, Nobel Laureate'

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Renato Dulbecco, Nobel Laureate. Science, 7th
March 1986
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3 billion DNA bases in each set of chromosomes
and 2 sets of chromsomes, means 6 billion DNA
bases per cell
The secret book of humans took several years and
hundreds of millions of dollars to read, for the
first time, in 2001
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2009 The secret book of a breast cancer read in
its entirety for the first time, in a matter of
weeks.
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ER lobular breast cancer
PRIMARY TUMOUR
We asked the following question - How does the
genome sequence of a primary breast cancer differ
from a metastasis in the same patient, arising
years later?
9 YEAR INTERVAL
METASTATIC TUMOUR
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EVOLUTION OF MUTATIONS OVER 9 YEARS
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What did we conclude?
The primary breast cancer was heterogenous from
the start, ie. Not all of the cancer cells could
have contained the same mutations.
The primary breast cancer cells underwent
considerable evolution of their genomes over a 9
year interval
This has important implications for the way
therapeutic strategies should be developed - to
take into account from the very beginning, that
not all the cancer cells in a tumour have
necessarily the same mutations. This has
parallels with drug treatment strategies used in
HIV and malaria.
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Industrial-scale cloning and sequencing
DNA RNA
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Genome centre in-a-box
1 instrument 3,000,000,000 bp / day - reads are
short (eg 75 bp) - designed for re-sequencing
3,400 instruments 3,000,000,000 bp / day -
reads are long (eg gt750 bp) - designed for de
novo sequencing
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Clonal single molecule arrays
Attach single molecules to surface
Amplify to form clusters
Prepare DNA fragments
Ligate adapters
Sequence
20 microns
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Properties of cancer cells

• Evasion of programmed cell death
• Uncontrolled cell division
• Invasion of adjacent tissues
• Metastasize to distant sites
• Emergence of treatment resistant disease

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Current Illumina GAIIX throughput

• 24 billion raw base-pairs / 8 day run
• 20.4 billion base-pairs aligned
• Amount of sequence equivalent to 3 4 human
  genomes (diploid) per instrument each week.
• Human genome re-sequencing is on the verge of
  being routine.

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Cancer sequencing at the BC Cancer Agency

• Breast cancers
• Sam Aparicio, Karen Gelmon, Stephen Chia, Carlos
  Caldas (CRUK)
• Follicular and diffuse large B cell lymphomas
• J. Connors (Andy Mungall , Ryan Morin)
• Non small cell lung cancers
• Janessa Laskin
• Ovarian cancers
• David Huntsman
• Prostate cancers
• Mira Keyes
• Neuroblastoma
• David Kaplan (Toronto)
• Chemotherapy resistant colorectal cancer
• Isabella Tai
• Oligodendrogliomas
• Greg Cairncross and Sam Weiss

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Funding

• Genome Canada NCI - OCG (US)
• NCIC / TFF NHGRI (US)
• Genome BC NIEHS
• DOD (US) CIHR
• NSERC CBCRA
• CFI CBCF BC/Yukon
• MSFHR Donors
• PHSA BC Cancer Foundation

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Aghaeepour Nima Ally
Adrian An Jianghong
Armstrong Luke Aronshtam
Diana Asano Jennifer
Axam Heather Bala
Miruna Bilenky Mikhail
Birol Inanc Bosdet
Ian Brand Dana
Bretherick Karla Brooks-Wilson
Angela Brown-John Mabel
Butterfield Yaron Carlsen
Rebecca Castellarin Mauro
Cezard Timothee Chan
Simon Chan Annie
Chan Clinton Chan
Susanna Chand Steve
Charters Anita Cheng
Dean Cheng Grace
Cheung Dorothy Chin
Rodney Chittaranjan Suganthi
Chiu Readman Choe
Gina Chopra Vik
Chrisp Robert Chu
Andy Chuah Eric Chun
Hye-Jung Elizabeth Clark
Thomas Clarke Amanda
Clarke Louise Clement
Ainsley Coope Robin
Corbett Richard Cornean
Monica
Cortes Adrian Crisan
AnaMaria Crisostomo Lulu
Cruz Katty DSouza
Cletus Delaney Allen
Deng Athena Deng
Merinda DeVorkin Linsday
Dhalla Noreen Docking
Rod Dreolini Lisa
Drobnies Adrienne Dutt
Jessica Earp Madalene
Farnoud Noushin Fejes
Anthony Ferguson Cynthia
Field Matthew Flibotte
Stephane Fornika Dan
Freeman Doug Gillespie
Marilyn Glavas Natalie
Gorski Sharon Goya
Rodrigo Griffith Malachi
Griffith Obi Guin
Ranabir Ha Gavin
Hach Faraz Haile Merhu
Simon Halaschek-Wiener Julius
Hall Adam Hannigan
Adrienne Hardie Jennifer
He An Hilchey
Colin Hirst Carrie
Hirst Martin Holt
Robert Horspool Daniel
Hou Claire
Hunt Peter Hunter
Jayne Jackman Shawn
Jang Carrie Janoo-Gilani
Rozmin Jefferson Kelsey
Johnson Lindsey Johnson
Joanne Jones Steven
Kaminski Monica Kamoh
Baljit Kirk Heather
Kneller Julie Krzywinski
Martin Kwong Letticia
LHeureux Theresa Leach
Stephen Lee Darlene
Lee Hyun-Wu Lee
Stephanie Lee Tang
Leung Amy Leung
Amy O. Leung Didi
Li Yvonne Li
Irene Liao Nancy
Lim Raymond Ly
Shallom Ma Kevin
Ma Rita Mah
Diana Malhis Nawar
Marra Marco Matsuo
Corey Mawji Rina May
Lorraine Mayo
Michael McDonald Helen
McMurtrie Heather McPherson
Andrew Mead Carri-Lyn
Miao Lisa Miller
Diane
Moksa Michelle Moore
Richard Moradian
Annie Morin Gregg
Morin Ryan Morozova
Olena Morrissy Anca Sorana
Mungall Andy Mungall
Karen Munro Sarah
Myung Jae-Kyung Nielsen
Cydney Ning Kaida
Novik Karen Okada
Mark Palmquist Diana
Pandoh Pawan Pang
Johnson Paul Jessica
Peloso Irene Phan
Linh Piché Renée
Prabhu Anna-Liisa Pugh
Trevor Qian Jenny
Rahmani Maziar Ren
Jianhua Robertson Gordon
Roger Jennifer Roscoe
Robyn Ruschkowski Sharon
Sadar Marianne Santos
Roland Schein Jacquie
Schuetz Johanna Severson
Tesa Shafiei Ash
Shin Heesun Sleumer
Monica Slobodan Jared
Smailus Duane Smith
Jillian So Winnie
Sobel Richard
Stazyk Greg Suragh
Cecelia Sze Wing-Ka
Tai Isabella Tam
Angela Tam Bonny
Tam Teresa Tang
Michelle Taylor Greg
Teague Kevin Thiessen
Nina Thompson Amy
Thorne Christina Thorne
Ken Tomescu Anca
Totawar Parikshit Trinh
Eva Troussard Armelle
Tsai Miranda Tse
Kane Uyar Bora
Varhol Richard Volar
Milica Vollet Sarah
Wagner Susan Wang
Gang Wang Helena
Wang Jean Warren
René Wickrama Denil
Wiebe Nick Wilson
Gary Wong Kim Wong
Tina Woodsworth Daniel
Wright Ken Wu
Jackson Wye Natasja
Yang George Zeng
Thomas Zhang Chen
Zhao Yongjun
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Mutational evolution in a lobular breast tumour,
profiled at single nucleotide resolution
Departments of Molecular Oncology http//molonc.b
ccrc.ca Genome Sciences Centre http//www.bcgsc.ca
_at_ the BC Cancer Agency http//www.bccrc.ca