Hallmarks of Cancer: Promoting Mutations

A cell carries the entire set of genetic instructions – the genome – thatmakes an entire organism. The instructions are encoded in DNA as genes and packagedas chromosomes in the nucleus. DNA is not immutable and is subject to damageand mutations. Crucial changes in the genome affect the chance and rate of thedevelopment of a cancer cell.

Bruce Stillman
Cold Spring Harbor Laboratory

A characteristic of cancer cells is that those cells have changes in the natureof the genes that are compared to the normal cells. These changes can be eithermutations, or they can be deletion of whole genes, or they can be the additionof extra copies of genes. This is called genomic instability.

The changes in our genes that accumulate in cancer cells can be acquired by anumber of mechanisms. One is that during the process of copying the genetic information,mistakes can be made.

After the genetic information is copied, it has to be segregated to the two daughtercells. During that segregation process, it is often that the numbers of genesget distributed unevenly to those daughter cells.

A third way is that cancer cells have an inability to repair alterations in theDNA.

You need to acquire multiple changes in the genes, multiple genes, to get a full-blowncancer ∫ estimates to be about 5-7 genes perhaps on average. Those changesaccumulate over a period of time. Some of those changes accelerate the rate ofaccumulation of that. Whatís interesting is that some of them are inheritedahead of time. So BRCA-1 for instant, you are born with one of the niches alreadytaken out of your belt and then to accumulate the other 4 or 5 changes, youírealready on the way. And thatís why thereís a higher probabilityof getting cancer.