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Previous Volume 347:1593-1603 November 14, 2002 Number 20 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

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The development of cancer in humans involves a complex succession of events that usually occur over many decades. During this multistep process, the genomes of incipient cancer cells acquire mutant alleles of proto-oncogenes, tumor-suppressor genes, and other genes that control, directly or indirectly, cell proliferation. Different combinations of these mutant alleles are found in the genomes of the many distinct types of human cancer as well as in different cancers from the same tissue. An ever-increasing number of these genes have been shown to make contributions to the distinct steps involved in neoplastic transformation. The complexity of these observations provokes . . . [Full Text of this Article]

Multiple Alterations in the Genomes of Cells

Simple Transforming Systems

Collaborating Oncogenes in Rodent Cells

Further Complexity in the Transformation of Human Cells

Gene Silencing by Methylation of DNA

The Genetic History of Human Cancer

The Complexity of Tumor Pathogenesis

Colorectal Cancer

A Limited Number of Acquired Phenotypes in All Cancers

Genetic Instability

Disrupted Regulatory Circuits

            The Retinoblastoma Protein

            The p53 Protein

            Telomeres

            Mitogenic Stimulation

            Angiogenesis

Experimental Evidence of Key Regulatory Pathways

Introduction of Genes into Cultured Cells

Immortalization, Crisis, and Transformation

Emerging Rules Governing Human Cancer Development

Source Information

From the Department of Medical Oncology, Dana–Farber Cancer Institute, and the Department of Medicine, Brigham and Women's Hospital, Boston (W.C.H.); and the Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge (R.A.W.).

Address reprint requests to Dr. Hahn at the Department of Medical Oncology, Dana–Farber Cancer Institute, 44 Binney St., Boston, MA 02115, or at william_hahn@dfci.harvard.edu.

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