DNA Mutations alter a Cell`s Behavior
A cell is like a miniature factory in which each worker (protein) is responsible for carrying out a specific task for the good of the unit.
Every protein has its role. When a protein’s structure is changed by gene mutation, then the function of that protein is also changed. Some mutations cause a protein’s capabilities to be enhanced, like a weight lifter on steroids, whereas others cause its role to be lost entirely.
A critical breakthrough in our understanding of cancer was the discovery by Dr. J. Michael Bishop and Dr. Harold E. Varmus that mutations in the genes that control the normal growth patterns of a cell can transform these “good” genes into “bad” genes, which they termed oncogenes.
The study of oncogenes exploded after their findings, which were rewarded with the Nobel Prize. In contrast to normal genes, oncogenes spawn proteins that are supercharged at promoting growth, spread, and survival, cancer’s three essential properties. These overactive molecules are being targeted and quieted by new cancer-fighting drugs.
On the other hand, mutations to genes that serve as brakes on cancer growth and survival, called tumor suppressor genes, result in the loss of these important safeguards. Gatekeeper and caretaker genes are also types of tumor suppressor genes: by repairing mutations, they prevent cancer from developing. It is much harder to replace a lost tumor suppressor gene than it is to block an overactive oncogene. Replacement requires insertion of the lost gene into cells through a technique called gene therapy, whereas blocking is accomplished with drugs. To insert a gene into every cancer cell is a daunting technical task. As of this writing, there are no approved gene therapies for fighting cancer.
The combination of generating oncogenes and crippling tumor suppressor genes leads to a toxic imbalance in the cell that tips the balance in favor of uncontrolled growth. The result of all these mutations is a full-blown cancer cell. It is thought that a minimum of four mutations are needed to generate cancer, although most cancers contain far more.
For common cancers, such as prostate, breast, colon, and lung cancers, it takes many years for enough mutations to accumulate to give rise to cancer. This process is speeded up if an individual is born with a critical gene mutation.
The dependence of our DNA on the gatekeeper and caretaker security systems to prevent mutations is made crystal clear by what happens when these systems malfunction. Their breakdown is found in nearly all cancers and is believed to be one of the earliest changes in the process of converting a normal cell into a cancerous one. We have learned a great deal about these systems from families who have a hereditary predisposition to cancer. Inherited mutations in gatekeeper or caretaker genes are common in such families.
