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Sequence-based cancer genomics: progress, lessons and opportunities

Nature Reviews Genetics volume 4, pages 409–418 (2003)Cite this article

Key Points

  • The genomics revolution has catalysed the development of new technologies that can be applied to provide a comprehensive view of the molecular changes that occur during cancer development.

  • Three independent projects — the Cancer Genome Anatomy Project (CGAP), the Human Cancer Genome Project (HCGP) and the Cancer Genome Project (CGP) — have applied sequence-based technologies to produce synergistic data sets that are amenable to integration.

  • The data of these projects are derived from the human genome (through sequencing of gene exons to identify cancer mutations), as well as from the human transcriptome in the form of expressed sequence tags (ESTs) and serial analysis of gene expression (SAGE) tags that are generated from tumours and normal tissues.

  • The CGAP has facilitated the interface of the human genome sequence with the cytogenetic map through FISH-mapping of BAC clones that were substrates for generating the finished genome sequence. This linkage facilitates the characterization of chromosomal aberrations that are associated with cancer.

  • A suite of informatics tools is accessible through the CGAP website that allow in silico analysis of CGAP and HCGP gene-expression data, polymorphisms and chromosomal aberrations of cancer. In the future, these data sets will be integrated with the mutation analysis of the CGP.

  • The data sets that are generated by these projects are a platform for a variety of applications in cancer research, such as the design and generation of microarrays.

Abstract

Technologies that provide a genome-wide view offer an unprecedented opportunity to scrutinize the molecular biology of the cancer cell. The information that is derived from these technologies is well suited to the development of public databases of alterations in the cancer genome and its expression. Here, we describe the synergistic efforts of research programmes in Brazil, the United Kingdom and the United States towards building integrated databases that are widely accessible to the research community, to enable basic and applied applications in cancer research.

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Figure 1: The contribution of sequence-based genomic data to cancer research.

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Acknowledgements

R.L.S. thanks R. Klausner for initiating the Cancer Genome Anatomy Project and for vigorous encouragement and support during the implementation. A.J.G.S. is indebted to F. Perez and L. Old, respectively the Scientific Directors of the State of São Paulo Research Foundation (FAPESP) and the Ludwig Institute for Cancer Research, for their enthusiastic support of the Human Cancer Genome Project. R.W. thanks M. Stratton, A. Futreal and the Wellcome Trust.

Author information

Authors and Affiliations

  1. National Cancer Institute, 31 Center Drive, Room 10A07, Bethesda, 20892, Maryland, USA

    Robert L. Strausberg

  2. Ludwig Institute for Cancer Research, 605 Third Avenue, New York, 10158, USA

    Andrew J. G. Simpson

  3. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, Cambridge, UK

    Richard Wooster

Authors
  1. Robert L. Strausberg
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Correspondence to Robert L. Strausberg.

Related links

Related links

DATABASES

LocusLink

ABL

ARAF1

BCR

BRAF

BRCA1

BRCA2

RAF1

OMIM

chronic myeloid leukaemia

FURTHER INFORMATION

Cancer Genome Anatomy Project

Cancer Genome Project

dbEST

Gene Expression Omnibus

Human Cancer Genome Project

IMAGE Consortium

Mitelman Database of Chromosome Aberrations in Cancer

SAGE Genie

SAGEmap

Spectral Karyotyping/Comparative Genomic Hybridization Database

Glossary

TRANSCRIPTOME

The complete catalogue of all the RNA species of a cell, tissue or organism.

cDNA

Complementary DNA that is produced from an RNA template by an RNA-dependent DNA polymerase

HYPOXIA

A physiological state in which insufficient oxygen reaches a tissue.

FLUORESCENCE IN SITU HYBRIDIZATION

(FISH). A technology in which chromosomes (or chromosomal segments) are painted with fluorescent molecules.

BACTERIAL ARTIFICIAL CHROMOSOME

(BAC). A DNA molecule that can be propagated in bacteria and is useful for cloning large (100–200 kb) segments of DNA from other species.

PHASE I TRIAL

The first stage in a clinical trial, which is designed to assess the safety and dosage levels of a new treatment, and usually involves only a few patients.

BLAST CRISIS

The progression of myeloid leukaemia from a clonal proliferation of myeloid cells to a highly refractory progressive disease with >30% blast cells in the peripheral blood and bone marrow, and a one-year survival of <10%.

HETERODUPLEX ASSAY

A rapid method to detect mutations that relies on the fact that double-stranded DNA molecules with a single base-pair mismatch migrate to a different location compared with molecules that do not have a mismatch.

PASSENGER ALTERATIONS

A phenomenon that refers to the fact that some mutations do not seem to have any functional benefit for the tumour; they probably arise owing to faulty DNA-repair machinery in the tumour, and are 'just along for the ride'.

COMPARATIVE GENOMIC HYBRIDIZATION

(CGH). A technology through which tumour and reference DNA are differentially labelled to show copy-number changes in tumour genomes

SPECTRAL KARYOTYPING

(SKY). A technique for painting each chromosome in a different colour, which is useful for looking at chromosomal aberrations such as translocations.

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Strausberg, R., Simpson, A. & Wooster, R. Sequence-based cancer genomics: progress, lessons and opportunities. Nat Rev Genet 4, 409–418 (2003). https://doi.org/10.1038/nrg1085

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