Tumorigenesis
 
Mutations in these three classes of genes can occur in the germline, resulting in hereditary predispositions to cancer, or in single somatic cells, resulting in sporadic tumors. The first somatic mutation in an oncogene or tumor-suppressor gene initiates the neoplastic process by generating a clonal cellular expansion – a collection of cells generated from a single progenitor cell that are genetically identical. Subsequent somatic mutations result in additional rounds of clonal expansion, and thus tumor progression. Indeed, the best modern definition of a neoplastic cell is one that has clonally expanded as a result of somatic mutations. Germline mutations of these genes cause cancer predisposition, not cancer per se: people with these mutations have a ‘head start’ on the neoplastic process, as a mutation that can contribute to cancer is already present in every one of their cells. Such individuals therefore often develop multiple tumors that occur at an earlier age than in individuals whose cancer-gene mutations have all occurred somatically. In people with these syndromes, only a very small fraction of the total cells in an at-risk organ become neoplastic because other (somatic) mutations are required to develop a clinically significant lesion.
 
How Does Genetic Information Guide Treatment?
 
Genotyping, the identification of genetic abnormalities, has been influencing treatment the treatment of brain tumors for the last decade. This is especially true for oligodendroglioma (Louis et al., 2002). Approximately 60% of anaplastic oligodendrogliomas respond to a chemotherapy regimen of PCV (procarbazine, CCNU, and vincristine) – an alkylating agent. Genotyping can be used to predict which group of patients will fall into this

Figure 1: Oligodendroglioma grade II (WHO) with LOH 1p and 19q. (A) H&E stain showing the typical "fried egg" appearance. (H&E stain). (B) Fluorescence In Situ Hybridization (FISH) for Chromosome 1p: The cells show 1 red signal and 2 green signals indicating a deletion of 1p36. (C) FISH for chrosome 19q: The cells show 1 green signal and 2 red signals indicating a deletion of 19q13.

Genetic Engineering: 1965 – 1985