Tumors are usually of clonal origin, that is, they arise from a single cell. The monoclonality of tumors can be seen, for example, in multiple myeloma, a tumor of the plasma cells. In serum protein electrophoresis, antibodies migrate mainly in the gamma globulin fraction. Antibodies are produced by a large number of different plasma cell clones. The antibodies produced by the various clones differ in their amino acid sequence and therefore also in the electrophoretic migration. The gamma globulins therefore represent a broad fraction. With a few exceptions, cells of a multiple myeloma have retained the property of normal plasma cells for the production of immunoglobulins. In patients with multiple myeloma, the electrophoresis of the serum proteins shows a narrow-base peak in the area of the g-globulin fraction. This is caused by a structurally uniform g-globulin, which is formed by the malignant plasma cell clone. The production of identical antibody molecules is therefore called monoclonal gammopathy.
The concept of clonal tumor evolution was developed by Peter Nowell. The concept is based on the basic principles of the classical theory of evolution, which Charles Darwin developed in the mid-19th century to explain the origin of biological species. Applied to the development of tumors, this concept means that the cell of origin of a tumor is hit by an event, usually by the mutation in a tumor gene, which confers a growth advantage over the normal cell population. This causes the cell to expand into a clone of identical cells when the host’s control mechanisms permit. A cell from this clone is hit by a second event, which again results in a growth advantage. This sequence is repeated until a cell finally grows into a tumor that escapes the control mechanisms of the host. In this model of clonal evolution, the cell of an expanding clone is accidentally hit by an event which confers a growth advantage. Under limiting environmental conditions (e.g. lack of oxygen and nutrients) the “stronger cell clones” can prevail against the “weaker cell clones”.
Assuming that the cell of origin of a tumor is a tissue stem cell and that this cell gives rise to the tumor, the original concept of clonal evolution has to be modified. According to this concept, the cell of origin of the tumor, namely the somatic stem cell, is hit by an event, which, in the subsequent cell populations, disturbs the balance between proliferation, apoptosis and differentiation resulting in an increased cell number. This is usually associated with an altered, immature phenotype of the tissue. The tumor stem cell is subsequently hit by additional events, which eventually lead to a malignant tumor that grows invasively and spreads metastases in regional lymph nodes and distant organs.
