This blog is part 3 of 4 of our "Gene" Fridays series on cancer genetics.
To help people understand the complexity of cancer and the series of genetic events that lead to its formation, Dr. Bert Vogelstein built upon the encyclopedia analogy. “Each of us has an encyclopedia in our cells, and each page of that encyclopedia represents one gene,” explains Dr. Vogelstein. A set of genetic encyclopedias is comprised of 46 books, and each of these books represents chromosomes—23 books are inherited from our mother and 23 are inherited from our father. Each “chromosome” book has about 1,000 pages—one for each gene on that chromosome. Every page is filled with about 1500 letters. However, the letters on the “gene” pages are not the 26 A through Z alphabet characters. Rather, just four characters represent the “gene” alphabet: A, C, G, and T, an abbreviation for the chemicals that make up genes.
Mistakes that occur in this genetic encyclopedia are like transposed letters. For example, if a book contains letters to form the word “feet,” it means one thing to the reader. If two letters are transposed, and the word appears as “fete,” it means something altogether different. The same is true of the characters that make up the genetic alphabet. The cancer cell genome may have an “A” instead of a “C” or a “G” instead of a “T.” This, he says is a mutation, and when they occur, it changes the way a cell interprets its instructions, and as a result, how it behaves.
A few other errors can occur. Sometimes a page is repeated, in a process known as gene amplification. In other cases, the page is missing. This is a genetic deletion. Dr. Vogelstein says of these possible errors, by far the most common is the typographical character transpositions known as mutations.
Save for these approximate 50 errors among the millions of characters that make up the genes, cancer cells are nearly identical to normal cells, and that is what makes cancer such a complex disease. Teasing out these errors from a sea of normal cells confounds both scientists and the human body’s own checks and balances.
Consider bacteria, says Dr. Vogelstein. Bacterial infections are easily recognized by the body’s immune system and treatable with drugs known as antibiotics. The reason, he says, is that bacterial genomes are vastly different than the human genome. Bacteria have 1,000 to 2,000 genes as opposed to the 20,000 or so genes in the human genome. These differences make it possible to develop drugs that target genes made by bacteria and impact infections without affecting the genes of human cells.
“In cancer, 19,950 genes are the same in most cases, and the other 50 have just slight changes to distinguish them from normal cells,” says Dr. Vogelstein. To further complicate matters, “Two cancers can be from the same organ, look similar under the microscope, but genetically they are distinct.” That is why therapies that work in one patient may not work in another.