title: Cancer genomics: technology, discovery, and translation.
abstract: In recent years, the increasing awareness that somatic mutations and other genetic aberrations drive human malignancies has led us within reach of personalized cancer medicine (PCM). The implementation of PCM is based on the following premises: genetic aberrations exist in human malignancies; a subset of these aberrations drive oncogenesis and tumor biology; these aberrations are actionable (defined as having the potential to affect management recommendations based on diagnostic, prognostic, and/or predictive implications); and there are highly specific anticancer agents available that effectively modulate these targets. This article highlights the technology underlying cancer genomics and examines the early results of genome sequencing and the challenges met in the discovery of new genetic aberrations. Finally, drawing from experiences gained in a feasibility study of somatic mutation genotyping and targeted exome sequencing led by Princess Margaret Hospital-University Health Network and the Ontario Institute for Cancer Research, the processes, challenges, and issues involved in the translation of cancer genomics to the clinic are discussed.
authors.affiliation: FRCPC, Princess Margaret Hospital, Drug Development Program, 610 University Ave, Ste 5-718, Toronto, Ontario, M5G 2M9, Canada.
authors.forename: Ben
authors.initials: B
authors.lastname: Tran
authors.forename: Janet E
authors.initials: JE
authors.lastname: Dancey
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: John D
authors.initials: JD
authors.lastname: McPherson
authors.forename: Philippe L
authors.initials: PL
authors.lastname: Bedard
authors.forename: Andrew M K
authors.initials: AM
authors.lastname: Brown
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Patricia
authors.initials: P
authors.lastname: Shaw
authors.forename: Nicole
authors.initials: N
authors.lastname: Onetto
authors.forename: Lincoln
authors.initials: L
authors.lastname: Stein
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
mesh_terms: D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D019295:Computational Biology; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D056726:Genetic Association Studies; D005821:Genetic Techniques / Q000941:ethics / Q000592:standards; D023281:Genomics / Q000941:ethics / Q000379:methods*; D060005:Genotyping Techniques; D059014:High-Throughput Nucleotide Sequencing; D016045:Human Genome Project; D006801:Humans; D008967:Molecular Biology / Q000379:methods / Q000592:standards; D009369:Neoplasms / Q000235:genetics*; D009864:Ontario; D014176:Protein Biosynthesis