Understanding the genetic changes in tumors

Cecile G. Tamura

Understanding the genetic changes in tumors that distinguish the most lethal cancers from more benign ones could help doctors better treat patients.

Researchers use a big-data approach to find links between different genes and patient survival.

To generate the atlas, researchers led by Mathias Uhlén, a professor of microbiology at the Royal Institute of Technology in Sweden, used a supercomputer to analyze 17 major types of human cancers from nearly 8,000 tumor samples. Uhlén says his team was looking for “holistic changes across the genome caused by these mutations.

They then mapped all the genes found in those cancer cells to find out how proteins made by these genes affect patient survival. Genes carry instructions for making proteins, and the level of gene expression increases or decreases the amount of protein that genes make. These resulting proteins can dramatically influence biological processes like cancer.

Types of genes linked to cancer

Many of the genes that contribute to the development of cancer fall into broad categories:

• Tumor suppressor genes are protective genes. Normally, they limit cell growth by monitoring how quickly cells divide into new cells, repairing mismatched DNA, and controlling when a cell dies. When a tumor suppressor gene is mutated, cells grow uncontrollably and may eventually form a mass called a tumor. BRCA1, BRCA2, and p53 are examples of tumor suppressor genes. Germline mutations in BRCA1 or BRCA2 genes increase a woman’s risk of developing hereditary breast or ovarian cancers. The most commonly mutated gene in people who have cancer is p53. In fact, more than 50% of all cancers involve a missing or damaged p53 gene. Most p53 gene mutations are acquired mutations. Germline p53 mutations are rare.
  
• Oncogenes turn a healthy cell into a cancerous cell. Mutations in these genes are not inherited. Two common oncogenes are:
  
• HER2, which is a specialized protein that controls cancer growth and spread, and it is found on some cancer cells, such as breast and ovarian cancer cells
  
• The ras family of genes, which make proteins involved in cell communication pathways, cell growth, and cell death.
  
• DNA repair genes fix mistakes made when DNA is copied. But if a person has an error in a DNA repair gene, these mistakes are not corrected. And then they become mutations, which may eventually lead to cancer. This is especially true if the mutation occurs in a tumor suppressor gene or oncogene. Mutations in DNA repair genes can be inherited, such as with Lynch syndrome, or acquired. 
  

Despite all that is known about the different ways cancer genes work, many cancers cannot be linked to a specific gene. Cancer likely involves multiple gene mutations. Some evidence also suggests that genes interact with their environment, further complicating genes’ role in cancer.
Doctors hope to continue learning more about how genetic changes affect the development of cancer. This knowledge may lead to improvements in finding and treating cancer, as well as predicting a person’s risk of cancer.