Carcinogenesis: The molecular basis for cancer

• Non-lethal genetic damage lies at the heart of carcinogenesis

  1. Mutation acquired by

     1. Environmental agents: chemicals, radiation, viruses

     2. Inheritance through the germ line: a tumor mass results from the clonal expansion of a single progenitor cell that has incurred genetic damage (i.e., tumors are monoclonal)

• Three classes of normal regulatory genes are the principal targets of genetic damage. They are:

  1. Growth-promoting protooncogenes

     1. Mutant alleles of protooncogenes are called oncogenes. They are considered dominant because they transform cells despite the presence of their normal counterpart.

  2. Growth-inhibiting cancer suppressor genes

     1. Both normal alleles of these tumor suppressor genes must be damaged for transformation to occur (recessive oncogenes)

  3. Genes that regulate apoptosis

     1. May be dominant or recessive

• DNA repair genes are important in carcinogenesis.

  1. They affect cell proliferation or survival indirectly by influencing the ability of the organism to repair non-lethal damage in other genes, including protooncogenes, tumor suppressor genes, and genes that regulate apoptosis.

  2. A disability in these genes can predispose to wide-spread mutations in the genome and to neoplastic transformation.

• Carcinogenesis is a multi-step process at both the phenotypic and genetic levels. (tumor progression)

Category: Pathology Notes