Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 331 (6024): 1553-1558

Copyright © 2011 by the American Association for the Advancement of Science

Exploring the Genomes of Cancer Cells: Progress and Promise

Michael R. Stratton*

Abstract: The description and interpretation of genomic abnormalities in cancer cells have been at the heart of cancer research for more than a century. With exhaustive sequencing of cancer genomes across a wide range of human tumors well under way, we are now entering the end game of this mission. In the forthcoming decade, essentially complete catalogs of somatic mutations will be generated for tens of thousands of human cancers. Here, I provide an overview of what these efforts have revealed to date about the origin and behavioral features of cancer cells and how this genomic information is being exploited to improve diagnosis and therapy of the disease.

Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

* E-mail: mrs{at}sanger.ac.uk

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing.
E. Heitzer, M. Auer, C. Gasch, M. Pichler, P. Ulz, E. M. Hoffmann, S. Lax, J. Waldispuehl-Geigl, O. Mauermann, C. Lackner, et al. (2013)
Cancer Res. 73, 2965-2975
   Abstract »    Full Text »    PDF »
Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms.
A. Malhotra, M. Lindberg, G. G. Faust, M. L. Leibowitz, R. A. Clark, R. M. Layer, A. R. Quinlan, and I. M. Hall (2013)
Genome Res. 23, 762-776
   Abstract »    Full Text »    PDF »
Single-cell paired-end genome sequencing reveals structural variation per cell cycle.
T. Voet, P. Kumar, P. Van Loo, S. L. Cooke, J. Marshall, M.-L. Lin, M. Zamani Esteki, N. Van der Aa, L. Mateiu, D. J. McBride, et al. (2013)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Laser capture microdissection-reduced representation bisulfite sequencing (LCM-RRBS) maps changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse.
M. Schillebeeckx, A. Schrade, A.-K. Lobs, M. Pihlajoki, D. B. Wilson, and R. D. Mitra (2013)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
The Scientific Drunk and the Lamppost: Massive Sequencing Efforts in Cancer Discovery and Treatment.
M. B. Yaffe (2013)
Science Signaling 6, pe13
   Abstract »    Full Text »    PDF »
Whole-Exome Sequencing Studies of Nonfunctioning Pituitary Adenomas.
P. J. Newey, M. A. Nesbit, A. J. Rimmer, R. A. Head, C. M. Gorvin, M. Attar, L. Gregory, J. A. H. Wass, D. Buck, N. Karavitaki, et al. (2013)
J. Clin. Endocrinol. Metab. 98, E796-E800
   Abstract »    Full Text »    PDF »
CUL3 and NRF2 Mutations Confer an NRF2 Activation Phenotype in a Sporadic Form of Papillary Renal Cell Carcinoma.
A. Ooi, K. Dykema, A. Ansari, D. Petillo, J. Snider, R. Kahnoski, J. Anema, D. Craig, J. Carpten, B.-T. Teh, et al. (2013)
Cancer Res. 73, 2044-2051
   Abstract »    Full Text »    PDF »
Diagnostic Cancer Genome Sequencing and the Contribution of Germline Variants.
O. Kilpivaara and L. A. Aaltonen (2013)
Science 339, 1559-1562
   Abstract »    Full Text »    PDF »
Arkadia Regulates Tumor Metastasis by Modulation of the TGF-{beta} Pathway.
M. A. Briones-Orta, L. Levy, C. D. Madsen, D. Das, Y. Erker, E. Sahai, and C. S. Hill (2013)
Cancer Res. 73, 1800-1810
   Abstract »    Full Text »    PDF »
Description of the Developmental Patterns of Epithelial Cells and Cancers Originating from Them Will Provide Many Sites for Therapy.
K. M. ANDERSON, P. GUINAN, and M. RUBENSTEIN (2013)
In Vivo 27, 159-163
   Abstract »    Full Text »    PDF »
Translesion DNA Synthesis and Mutagenesis in Eukaryotes.
J. E. Sale (2013)
Cold Spring Harb Perspect Biol 5, a012708
   Abstract »    Full Text »    PDF »
Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells.
W. Yang, J. Soares, P. Greninger, E. J. Edelman, H. Lightfoot, S. Forbes, N. Bindal, D. Beare, J. A. Smith, I. R. Thompson, et al. (2013)
Nucleic Acids Res. 41, D955-D961
   Abstract »    Full Text »    PDF »
Cisplatin Selects for Multidrug-Resistant CD133+ Cells in Lung Adenocarcinoma by Activating Notch Signaling.
Y.-P. Liu, C.-J. Yang, M.-S. Huang, C.-T. Yeh, A. T. H. Wu, Y.-C. Lee, T.-C. Lai, C.-H. Lee, Y.-W. Hsiao, J. Lu, et al. (2013)
Cancer Res. 73, 406-416
   Abstract »    Full Text »    PDF »
Copy-number-aware differential analysis of quantitative DNA sequencing data.
M. D. Robinson, D. Strbenac, C. Stirzaker, A. L. Statham, J. Song, T. P. Speed, and S. J. Clark (2012)
Genome Res. 22, 2489-2496
   Abstract »    Full Text »    PDF »
Analysis of mRNA Profiles after MEK1/2 Inhibition in Human Pancreatic Cancer Cell Lines Reveals Pathways Involved in Drug Sensitivity.
S. Gysin, J. Paquette, and M. McMahon (2012)
Mol. Cancer Res. 10, 1607-1619
   Abstract »    Full Text »    PDF »
Comparative analysis of somatic copy-number alterations across different human cancer types reveals two distinct classes of breakpoint hotspots.
Y. Li, L. Zhang, R. L. Ball, X. Liang, J. Li, Z. Lin, and H. Liang (2012)
Hum. Mol. Genet. 21, 4957-4965
   Abstract »    Full Text »    PDF »
Loss of SNAIL Regulated miR-128-2 on Chromosome 3p22.3 Targets Multiple Stem Cell Factors to Promote Transformation of Mammary Epithelial Cells.
P. Qian, A. Banerjee, Z.-S. Wu, X. Zhang, H. Wang, V. Pandey, W.-J. Zhang, X.-F. Lv, S. Tan, P. E. Lobie, et al. (2012)
Cancer Res. 72, 6036-6050
   Abstract »    Full Text »    PDF »
Whole-Exome Sequencing Studies of Nonhereditary (Sporadic) Parathyroid Adenomas.
P. J. Newey, M. A. Nesbit, A. J. Rimmer, M. Attar, R. T. Head, P. T. Christie, C. M. Gorvin, M. Stechman, L. Gregory, R. Mihai, et al. (2012)
J. Clin. Endocrinol. Metab. 97, E1995-E2005
   Abstract »    Full Text »    PDF »
The Global Cancer Genomics Consortium: Interfacing Genomics and Cancer Medicine.
The Global Cancer Genomics Consortium (2012)
Cancer Res. 72, 3720-3724
   Abstract »    Full Text »    PDF »
Oncogenic cooperation between SOCS family proteins and EGFR identified using a Drosophila epithelial transformation model.
H. Herranz, X. Hong, N. T. Hung, P. M. Voorhoeve, and S. M. Cohen (2012)
Genes & Dev. 26, 1602-1611
   Abstract »    Full Text »    PDF »
DNA Methylation As a Clinical Marker in Oncology.
J.-P. Issa (2012)
J. Clin. Oncol. 30, 2566-2568
   Full Text »    PDF »
Attacking a Nexus of the Oncogenic Circuitry by Reversing Aberrant eIF4F-Mediated Translation.
P. B. Bitterman and V. A. Polunovsky (2012)
Mol. Cancer Ther. 11, 1051-1061
   Abstract »    Full Text »    PDF »
Predictive Biomarkers in Advance of a Companion Drug: Ahead of Their Time?.
R. K. Kelley, C. Atreya, A. P. Venook, and P. G. Febbo (2012)
J Natl Compr Canc Netw 10, 303-309
   Abstract »    Full Text »    PDF »
Order-of-magnitude Estimates of Latency (Time to Appearance) and Refill Time of a Cancer from a Single Cancer 'Stem' Cell Compared by an Exponential and a Logistic Equation.
K. M. ANDERSON, M. RUBENSTEIN, P. GUINAN, and M. PATEL (2012)
In Vivo 26, 183-189
   Abstract »    Full Text »    PDF »
VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing.
D. C. Koboldt, Q. Zhang, D. E. Larson, D. Shen, M. D. McLellan, L. Lin, C. A. Miller, E. R. Mardis, L. Ding, and R. K. Wilson (2012)
Genome Res. 22, 568-576
   Abstract »    Full Text »    PDF »
Detecting genomic indel variants with exact breakpoints in single- and paired-end sequencing data using SplazerS.
A.-K. Emde, M. H. Schulz, D. Weese, R. Sun, M. Vingron, V. M. Kalscheuer, S. A. Haas, and K. Reinert (2012)
Bioinformatics 28, 619-627
   Abstract »    Full Text »    PDF »
Exploiting the Mutanome for Tumor Vaccination.
J. C. Castle, S. Kreiter, J. Diekmann, M. Lower, N. van de Roemer, J. de Graaf, A. Selmi, M. Diken, S. Boegel, C. Paret, et al. (2012)
Cancer Res. 72, 1081-1091
   Abstract »    Full Text »    PDF »
Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways.
J. Wu, Y. Jiao, M. Dal Molin, A. Maitra, R. F. de Wilde, L. D. Wood, J. R. Eshleman, M. G. Goggins, C. L. Wolfgang, M. I. Canto, et al. (2011)
PNAS 108, 21188-21193
   Abstract »    Full Text »    PDF »
Correct End Use during End Joining of Multiple Chromosomal Double Strand Breaks Is Influenced by Repair Protein RAD50, DNA-dependent Protein Kinase DNA-PKcs, and Transcription Context.
A. Gunn, N. Bennardo, A. Cheng, and J. M. Stark (2011)
J. Biol. Chem. 286, 42470-42482
   Abstract »    Full Text »    PDF »
100 years of Rous sarcoma virus.
R. A. Weiss and P. K. Vogt (2011)
J. Exp. Med. 208, 2351-2355
   Abstract »    Full Text »    PDF »
The early history of tumor virology: Rous, RIF, and RAV.
H. Rubin (2011)
PNAS 108, 14389-14396
   Abstract »    Full Text »    PDF »
The Death of the Cancer Cell.
C. Sonnenschein and A. M. Soto (2011)
Cancer Res. 71, 4334-4337
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882