title: Molecular mechanisms of human carcinogenesis.
abstract: Intensive research efforts during the last several decades have increased our understanding of carcinogenesis, and have identified a genetic basis for the multi-step process of cancer development. Tumors grow through a process of clonal expansion driven by mutation. Several forms of molecular alteration have been described in human cancers, and these can be generally classified as chromosomal abnormalities and nucleotide sequence abnormalities. Most cancer cells display a phenotype characterized by genomic hypermutability, suggesting that genomic instability may precede the acquisition of transforming mutations in critical target genes. Reduced to its essence, cancer is a disease of abnormal gene expression, and these genetic abnormalities contribute to cancer pathogenesis through inactivation of negative mediators of cell proliferation (including tumor suppressor genes) and activation of positive mediators of cell proliferation (including proto-oncogenes). In several human tumor systems, specific genetic alterations have been shown to correlate with well-defined histopathological stages of tumor development and progression. Although the significance of mutations to the etiological mechanisms of tumor development has been debated, a causal role for such genetic lesions is now commonly accepted for most human cancers. Thus, genetic lesions represent an integral part of the processes of neoplastic transformation, tumorigenesis, and tumor progression, and as such represent potentially valuable markers for cancer detection and staging.
authors.affiliation: Department of Pathology and Laboratory Medicine, Curriculum in Toxicology, UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill NC, 27599, USA. william.coleman@pathology.unc.edu
authors.forename: William B
authors.initials: WB
authors.lastname: Coleman
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*