Germline and Somatic Variants: What Is the Difference?

January 14, 2020 by Suzanne M. Mahon DNS, RN, AOCN®, AGN-BC, FAAN

Somatic Variants

Somatic (https://www.ons.org/genomics-taxonomy/variant-subcategories#somatic) or acquired genomic (https://www.ons.org/genomics-taxonomy/genome-foundations) variants are the most common cause of cancer, occurring from damage to genes in an individual cell during a person’s life. They are classified (https://voice.ons.org/news-and-views/what-is-a-genomic-variant) in terms of the actionability of an available effective therapy. Cancers that occur because of somatic variants are referred to as sporadic cancers. Somatic variants are not found in every cell in the body, and they are not passed from parent to child. Some common carcinogens that cause pathogenic variants include tobacco use, ultraviolet light or radiation, viruses, chemical exposures, and aging.

Germline Variants

Germline variants (https://www.ons.org/genomics-taxonomy/genome-foundations#germline) are far less common, accounting for only about 5%–10% of all cancers. A germline variant 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 pathogenic variant from the initial sperm or egg cell is copied into every cell in the body. Because the pathogenic variant affects reproductive cells, it can pass from generation to generation.

Cancers caused by germline pathogenic variants are called inherited or hereditary. More than 50 different hereditary cancer syndromes (https://doi.org/10.1038/gim.2014.147) have been identified that can be passed from one generation to the next. Family and personal histories suggestive of germline pathogenic variants include:

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 (https://doi.org/10.1101/cshperspect.a036590). Some changes may be the result of cancer cells dividing, rather than the initiating event that led to the cancer’s development. As the cancer continues to grow, additional changes will occur, even within the same tumor.

A form of biomarker testing, DNA sequencing may identify both germline and somatic pathogenic variants by comparing the DNA sequence of cancer cells to healthy cells. Germline pathogenic variants are identified through a blood sample or with buccal cells from a saliva sample. Somatic variants are detected by either testing the tumor directly or liquid biopsy of a blood sample with circulating tumor cells to identify the DNA sequencing changes driving tumor growth. Understand the variants for a particular malignancy may help providers determine which therapies might be most effective.

Information provided by germline and somatic biomarker testing may overlap (https://cjon.ons.org/cjon/24/6/tumor-genomic-testing-identifying-characteristics-associated-germline-risk-developing). For example, a person with a malignancy harboring a BRCA pathogenic variant may or may not have an inherited BRCA germline variant. Depending on the cancer type, both tumor and germline testing may be used to help select treatment options. Patients should be referred for germline testing if they have a personal or family history suggestive of hereditary risk, the tumor has microsatellite instability, the variant is a cancer susceptibility gene, the gene is considered pathogenic or likely pathogenic, or the allele frequency approaches 50% (https://doi.org/10.1101/cshperspect.a036590).

What Oncology Nurses Need to Know

Oncology nurses should understand when to refer patients for germline testing and how to provide patient education about the difference between germline and somatic variants. Educating patients and families about the different types of variants enables patients to have insight into the development of cancer and what it means for their treatment and recommendations for prevention and early detection of other cancers.

During an already confusing and stressful time, patients and families may have trouble coping with both a cancer diagnosis and learning about germline risk because of the possibility that other family members may also have a hereditary susceptibility to develop malignancy. Knowledge of germline pathogenic variants allows nurses to guide the entire family on appropriate cancer prevention and early detection strategies.


Copyright © 2020 by the Oncology Nursing Society. User has permission to print one copy for personal or unit-based educational use. Contact pubpermissions@ons.org for quantity reprints or permission to adapt, excerpt, post online, or reuse ONS Voice content for any other purpose.