The Somatic Mutation Hypothesis

According to this hypothesis cancer is the result of somatic mutations, without viral infection occurring in a cell. Such a mutation may alter the control mechanism of the cell, leading to unregulated division or cancer. The mutations may involve the activation of normally repressed genes. This could take place by (i) mutations in the repressed genes themselves, or (ii) mutations that block the production of repressor proteins, thus unblocking inactive genes and making them active.

Most cancerous cells have abnormal chromosomal components. Often there are different numbers of chromosomes in different cells of one tumor. Such chromosomes are called philadelphia chromosomes. Chromosomal abnormality is found in the bone marrow of 90 per cent patients suffering from chronic myeloid leukemia. An elongated chromosome number 9 has also been reported from chronic myeloid leukemia patients. Possibly a piece has broken off from chromosome number 22 and translocated to number 9. In patients with retinoblastoma the middle segment of chromosome 13 is missing. It is possible, however, that the cases mentioned above could be the consequences or accompaniments of cancer rather than its cause. The evidence for chromosomal alteration as a cause of cancer does not look strong. Sachs and his group have postulated that cells contain effector (E) chromosomes which cause malignancy and suppressor (S) chromosomes which suppress malignancy. Whether a cell is malignant or not depends upon a balance in the number of E and S chromosomes. Chromosomal changes in hamster cells after treatment with polycyclic aromatic hydrocarbons (PAH) suggest that the modifications may be important in oncogenic transformation. At present the role of chromosomal changes in malignant transformation is debatable.