Cancer Genome Variation in Children,
Adolescents, and Young Adults*
Thomas J. Hudson, MD
This mini-review describes the rapid changes in genome technologies that are leading to comprehensive views of
genetic alterations in cancer, and presents high-level thoughts on ways to accelerate translation into clinical medicine.
Issues that are more relevant to children, adolescents, and young adult patients with cancer are highlighted. Cancer
2011;117(10 suppl):2262–7. V
C 2011 American Cancer Society.
KEYWORDS: cancer genomes, human genome, somatic mutations, cancer genetics, pediatric cancer, adolescent
cancer, young adult cancer, pharmacogenomics, pharmacogenetics, whole genome sequencing.
Each cancer patient is distinct with regard to clinical, familial, socioeconomic, environmental, and many other macro-
scopic factors. At the microscopic level, all cancer patients vary with regard to the DNA inherited from their parents and
DNA within their tumors, the latter resulting from acquired (or somatic) mutations because of carcinogens and abnormal
DNA repair mechanisms that frequently occur in cancer cells. Although the individuality of patients with cancer has
always been recognized, the fundamental uniqueness of each cancer genome, and the importance that this may have in the
clinical management of patients, has only been recognized in the latter half of the 20th century, initially as a result of cyto-
genetics1,2and then gradually at the molecular level based on the study of specific genes,3,4and today as a result of whole
cancer genome sequencing. The implications of this increased understanding of cancer as a complex and heterogenenous
disease involving mutations in hundreds or thousands of genes has led to a new paradigm in cancer research and manage-
ment coined ‘‘personalized medicine.’’ The National Cancer Institute (NCI) in the United States defines personalized
medicineas‘‘a formofmedicinethatuses information aboutaperson’sgenes,proteins,and environment toprevent,diag-
nose, and treat disease.’’ A few examples of personalized medicine have already reached the clinical setting, such as trastu-
zumabforsomeformsof breastcancer5and imatinibforleukemias6,7thatdisplayspecific geneticabnormalities.
Technological advances and large directed efforts allowing comprehensive studies of genomes in cancer patients
and/or tumors have accelerated the search forgenes and mutationsimplicated inthe etiology of cancer and progressionto-
platforms that evolved from vertical gel electrophoresis with a capacity of approximately 1000 nucleotide bases per day to
capillary instruments that yielded over 1 million bases per day. Since the release of the first draft of the human genome
sequence,8the capacity has kept improving at a breathtaking pace, with several instruments currently generating in excess
of 10 billion bases per day. These advances have been accompanied by drastic decreases in the cost of human genome
sequencing. Current estimates of reagent costs for a whole genome sequence in 2010 are approximately $10,000 US dol-
atacostof <$1000in afewyears. Othertechnologiestostudygenomeshave alsoevolvedrapidly.
Germline Genome Variation and Cancer
Before the release of the first human genome reference sequence in 2001, approximately 30 tumor suppressor genes and
100 dominant oncogenes had been identified.9Many of these were identified by mapping strategies in families having
DOI: 10.1002/cncr.26049, Received: September 20, 2010; Revised: November 17, 2010; Accepted: November 18, 2010, Published online April 27, 2011 in Wiley
Online Library (wileyonlinelibrary.com)
Corresponding author: Thomas J. Hudson, MD, Ontario Institute for Cancer Research, MaRS Centre, South Tower, 101 College St, Suite 800, Toronto, ON,
Canada M5G 0A3; Fax: (416) 673-6664; email@example.com
Ontario Institute for Cancer Research, Toronto, Ontario, Canada
The articles in this supplement represent presentations and discussions at the ‘‘International Workshop on Adolescents and Young Adults with Cancer: Towards
Better Outcomes in Canada’’ that was held in Toronto, Ontario, March 11-13, 2010.
*Workshop on Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada, Supplement to Cancer.
May 15, 2011
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Genomes of Early Onset Cancers/Hudson
May 15, 2011