Assessing Germline, Somatic Genetic Testing for Prostate Cancer

Among somatic mutations, approximately 89% of patients with metastatic castration-resistant prostate cancer have a potentially actionable mutation.

The development of gene therapy and targeted therapy for prostate cancer has been a significant breakthrough in the treatment of the most prevalent malignancy in men, explained Seon Jo Park, PharmD, BCOP, a clinical pharmacy specialist at Allegheny Health of the Network Cancer Institute, during a session at the Hematology/Oncology Pharmacy Association 2021 Virtual Annual Conference.

“If you look at the statistics, you see that there’s a startling number of patients who get diagnosed and die from their severe malignancy. Knowing that the family history and certain gene mutations increases the risk of prostate cancer, we are very excited to see more gene mutation research,” Park said during the session. “A lot of people will benefit from this research.”

For the purpose of framing the gene mutations within pancreatic cancer, Park explained that genes are contained within chromosomes, which are themselves contained within the cell nucleus. Conversely, a chromosome contains hundreds of thousands of genes.

In normal human cells, each individual cell contains 23 pairs of chromosomes for a total of 46. Within the chromosomes, the genes themselves consist of DNA, which hold the blueprint for the synthesis of protein.

In this way, germline DNA mutations specifically refer to the DNA that is the result of the unique combinations of genetic material within the DNA, half of which is from an individual’s mother and the other half from their father, Park noted.

Furthermore, germline genetic testing is able to identify the presence of inherited pathogenic mutations. Testing can be performed on lymphocyte DNA from blood or a combination of lymphocyte DNA and buccal cells from saliva. This is possible because germline DNA is nearly identical in all nucleated cells of an individual.

However, in contrast to germline mutations, somatic mutations are observed in tumor tissue from primary or metastatic site or blood, which also means that the mutation can change over time due to genetic instability and selected pressure from therapy. For this reason, repeated testing of tumor DNA may be necessary during the disease course to track such changes.

Germline mutations also vary in occurrence based on cancer subtype. After assessing the data, the investigators found that 11.8% to 16.2% of germline mutations occurred in metastatic prostate cancer, compared to 4.6% in localized prostate cancer, and approximately 2% to 3% in the general population who do not have prostate cancer, according to Park.

“They definitely found a higher prevalence of mutation in metastatic prostate cancer. The most common gene mutations they found were BRCA2, ATM, and CHEK2. They also found some mismatched repair mutations, such as MSH2 and MSH6 mutations,” Park said during the session.

Among the somatic mutations, approximately 89% of patients with metastatic castration-resistant prostate cancer have a potentially actionable mutation. Additionally, Park noted that these potentially actionable mutations can occur among both germline and somatic mutations.

There are 3 guidelines that give recommendations regarding germline testing: the Philadelphia Prostate Cancer Consensus (PPCC), the National Comprehensive Cancer Network guidelines for patients with prostate cancer, and the European Advanced Prostate Cancer Consensus. These guidelines all make recommendations that help clinicians make decisions regarding when to pursue germline mutation testing based on a patient’s family history.

The PPCC guideline specifically provided clarity on what constitutes a strong family history requiring germline mutation testing. First, they noted this testing was important to pursue for men with 1 brother or father or more than or equal to 2 male relatives who either were diagnosed with prostate cancer at an age younger than 60 years, died of prostate cancer, or had metastatic prostate cancer.

Second, the PPCC noted that patients with 2 or more relatives on the same side of the family who had hereditary breast and ovarian cancers or Lynch syndrome should pursue germline testing as well.

In terms of disease and tumor characteristics, all of the guidelines recommended patients who have metastatic prostate cancer have germline testing done. Additionally, for germline mutations, all of the guidelines strongly recommended patients with BRCA mutations and MMR genes have the test done.

For somatic tumor testing, they also recommended all of the patients with metastatic prostate cancer to get this test conducted as well.

“If they happened to find any pathogenic mutations, such as BRCA1, BRCA2, ATM or CHEK2 mutations, they recommended to get confirmatory germline testing done based on the genetic counseling and family history,” Park said during the session.


Park SJ. Genetic Testing for Prostate Cancer. Presented at: Hematology/Oncology Pharmacy Association 2021 Virtual Annual Conference; April 15, 2021; virtual. Accessed April 16, 2021.