Germline vs somatic mutations

Testing for germline BRCA1/2 mutations has been available since the 1990s and is currently used to assess cancer risk and inform treatment decisions. More recently tumor testing for BRCA mutations has also become available.¹

A BRCA mutation can be either germline or somatic.¹

The DNA in any cell can be altered through environmental exposure to certain chemicals, ultraviolet radiation, other genetic insults, or even errors that occur during the process of replication. If a mutation occurs in a germline cell (one that will give rise to gametes, i.e., egg or sperm cells), then this mutation can be passed to an organism's offspring. This means that every cell in the developing embryo will carry the mutation. As opposed to germline mutations, somatic mutations occur in cells found elsewhere in an organism's body.²

With germline testing, variants in a patient’s germline that can be passed on to offspring can be identified.³ Germline mutations can be identified by analysing DNA in a blood or saliva sample.⁴ Among sequential patients with breast cancer, 10.7% were found to have a germline mutation in a gene that predisposes women to breast or ovarian cancer.⁵

Determination of a mutation being somatic in origin requires genetic profiling of cancer tissue and a positive tumour test result, as well as analysis of DNA from blood or saliva to rule out germline mutations.⁴ These mutations are found in ~3% of patients with breast cancer.⁶

A BRCA mutation can be either germline or somatic.⁷

Blood germline testing

A blood sample is taken from the patient and sent to an internal or external lab for DNA extraction. The DNA is processed and tested to determine the presence of germline BRCA mutation(s).³

*Tumour testing – A BRCA test can assess DNA directly from tumour cells, taken from a biopsy, to determine the presence of a mutation. This test can identify mutations of both somatic and germline origin, though is typically unable to distinguish the origin. If a mutation is found, a subsequent blood test is typically employed to determine if the mutation is in the germline.³

The field of genetic testing for breast cancer has evolved over the years. Originally single genes were sequenced, which was labor-intensive and expensive.⁸

Tumour Testing

When using tumor tissue DNA to detect BRCA1/2 variants, both germline and somatic BRCA1/2 mutations are identified, this facilitates a focused germline testing effort and an overall reduction in genetic testing. Formalin-fixed paraffin–embedded (FFPE) specimens may be used for BRCA1/2 mutation analysis this is likely to be the most widely available sample type.³