Cancer occurs from mutations, or harmful changes from an alteration in a gene’s DNA sequence. Most mutations involve changes in the order of the base pairs, including substitutions, deletions, additions, or shifts. Mutations can be divided into broad categories based on the tissue where they occur.

Somatic Mutations

Somatic or acquired mutations are the most common cause of cancer. These mutations occur from damage to genes in an individual cell during a person’s life. Cancers that occur because of somatic mutations are referred to as sporadic cancers. Somatic mutations are not found in every cell in the body and they are not passed from parent to child. Some common carcinogens that cause these mutations include tobacco use, ultraviolet radiation, viruses, chemical exposures, and aging.

Germline Mutations

Germline mutations are far less common. A germline mutation occurs in a sperm cell or an egg cell and is passed directly from a parent to a child at the time of conception. As the embryo grows into a baby, the mutation from the initial sperm or egg cell is copied into every cell in the body. Because the mutation affects reproductive cells, it can pass from generation to generation.

Cancer caused by germline mutations is called inherited or hereditary cancer. It accounts for about 5%–10% of all cancers. More than 50 different hereditary cancer syndromes have been identified that can be passed from one generation to the next. Family and personal histories suggestive of germline mutations include:

  • Early onset cancer (breast, colon, or endometrial cancer under age 50)
  • Rare cancers (male breast cancer)
  • Certain pathologies (triple-negative breast cancer)
  • More cancers in a family than would be expected by chance

See the sidebar for more red flags that might indicate germline risk.

Identifying the Difference

In general, cancer cells have more genetic changes than normal cells, but each person’s cancer has a unique combination of genetic alterations. Some of these changes may be the result of cancer cells dividing, rather than the initiating event that led to the development of the cancer. As the cancer continues to grow, additional changes will occur. Even within the same tumor, cancer cells may have different genetic changes.

DNA sequencing techniques can identify both germline and somatic mutations by comparing the sequence of DNA with that in normal cells. Germline mutations can be identified by utilizing a saliva sample that contains buccal cells or a blood sample. Genetic testing in the tumor can be utilized to identify genetic changes in cancer cells that may be driving the growth of an individual’s cancer. This information may help determine which therapies might be most effective for treating a particular malignancy. Information provided by germline and tumor testing may overlap. For example, a person with a malignancy who has a BRCA mutation in the tumor, may or may not have an inherited BRCA mutation. Germline testing will be necessary to determine if the mutation is inherited. Depending on the cancer type, both tumor and germline testing may be used to help select treatment options. Thus, tumor DNA sequencing can also suggest the presence of inherited mutations. Patients should be referred for germline mutation testing if they have a personal or family history suggestive of hereditary risk, the tumor has microsatellite instability, the gene in the tumor is a cancer susceptibility gene, the gene is considered pathogenic or likely pathogenic, or the allele frequency approaches 50%.

What Oncology Nurses Need to Know

Oncology nurses are challenged to know when to refer patients for germline testing and to explain the difference between germline and somatic genetic changes and that germ­line changes can be present in tumors. This is confusing and stressful for patients and families, especially if tumor testing suggests germline risk because patients must cope not only with a cancer diagnosis but also the possibility that other family members have a hereditary susceptibility to develop malignancy. Genetic testing can also be lifesaving and reduce the morbidity and mortality associated with malignancy when information about somatic genetic changes guides treatment choices and knowledge of germline mutations identifies individuals at risk for developing malignancy and their appropriate cancer prevention and early detection strategies.