Understanding the Genomics and Genetics of Cancer

Biology Basics

The science and application of genomic testing in cancer begins at the cellular level. This requires understanding some of the basics about how normal cells function, what mutations are, how mutations lead to cancer and the components of a person’s genome, which includes all of the information needed for a person to develop and grow.

Components of a Cell

All living organisms and tissues of the body are made of cells, which are the smallest structure of the body capable of performing all of the processes that define life. Almost every cell in the human body contains a complete copy of the genome, which is a complete set of chromosomes containing the DNA code. These are the biological instructions for the types of cells in your body that make each person unique. DNA is passed from adults to their children.


A cell has three main parts:

  • The cell membrane surrounds the cell and controls the substances that go into and out of the cell. 
  • The nucleus is a structure inside the cell that contains most of the cell’s DNA. 
  • The cytoplasm is the fluid inside the cell. The cytoplasm is where most chemical reactions take place and where most proteins are made. 

A cell’s nucleus contains 46 chromosomes — 23 from your mother and 23 from your father. Each chromosome is made up of DNA, which consists of two twisting, paired strands (base pairs) that create a double helix. Base pairs are bonded to one another forming a “rung of the DNA ladder.”


Genes are sections of DNA on a chromosome that contain the instructions for making a specific protein that the body needs to function properly. Proteins are the basis of body structures, such as skin and hair, and of other substances such as enzymes, cytokines and antibodies. Each gene must have the correct instructions to make its protein.

How Healthy Cells Work

Healthy cells are created to perform specific functions in the body (see Figure 1). They exist for a period of time, reproducing themselves in an orderly fashion and dying off in a normal time frame when they become worn out or damaged.


Typically, cells divide after receiving specific signals from growth factors that circulate in the bloodstream or from a cell with which they are in direct contact. Once they receive the message to divide, the cells go through the cell cycle, a series of steps during which the chromosomes and other cell material double to make two copies. Checkpoints along each step of the process make sure that everything goes the way it should.


Many processes are involved in cell reproduction, and all these processes have to take place correctly for cells to divide properly. If anything goes wrong during this complicated process, cells may become cancerous.

How Cancer Develops

Cancer begins when genes start to change, or mutate, within the structure of normal cells. These cells – now called cancer cells – tend to grow out of control by ignoring signals to stop dividing. They do not die when they should, accumulating until they form a mass known as a tumor, which can be benign (noncancerous) or malignant (cancerous). Cancer can develop in almost any part of the body.


Unable to recognize their own natural boundaries, the cancer cells may spread to areas of the body where they do not belong. This is known as metastasis. Cancer can metastasize (spread) to other organs, tissues, bones or blood, but it is diagnosed according to where in the body it begins. If cancer starts in the lung, it is known as lung cancer. If it spreads to the brain, however, it is still considered lung cancer and is treated as such. It does not become brain cancer.


When cells mutate into cancer, the proteins those cells create are also abnormal. Cancer can affect protein production in the following ways:

  • Prevent some proteins from being made
  • Stop the protein from working the way it should
  • Keep the protein from working at all

Many of the genes associated with cancer development fall into three broad categories:

  1. Tumor suppressor genes normally control cell growth by monitoring how quickly cells divide into new cells, repairing mismatched DNA and controlling when a cell dies. When these genes mutate, cells can grow out of control and may form a tumor.
  2. Oncogenes turn healthy cells into cancerous cells and typically are not inherited. Two common oncogenes are HER2 and RAS.
  3. DNA repair genes fix the mistakes a cell makes when it divides and DNA is copied. When a cell cannot fix an error created when a cell is reproducing, mistakes may be copied into the new cell and not corrected. These mistakes can become mutations that lead to cancer. 

Understanding Mutations

Research has found that many cancers are caused by mutations (changes) in the DNA. It is common for a cell to have mutations, but it requires multiple mutations before a tumor is formed. A single mutation likely will not cause cancer.


A variety of mutations in a normal gene can increase a person’s risk of developing cancer. Mutations can occur in DNA, genes or chromosomes. Some mutations that can occur in genes include the following (see Figure 2):

Gene amplification — An increase in the number of copies of a gene, which is common in cancer cells. Some amplified genes may cause cancer cells to grow or become resistant to anticancer drugs.

Gene deletion — The loss of all or part of a gene.

Fusion gene — A gene made by joining parts of two different genes. Fusion genes, and the fusion proteins that come from them, may be made in the body when part of the DNA from one chromosome moves to another chromosome. Fusion proteins produced by this change may lead to the development of some types of cancer.

Overexpression — Too many copies of a protein or other substance, which may play a role in cancer development.

Rearrangement — A mutation that occurs in chromosomes where portions of the chromosome are not in order, which creates a new gene (not shown).

 

 

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