What is the significance of RET germline mutation found from Invitae next gen. liquid biopsy?

[Farmhand]

About six months ago I had peripheral blood drawn for Invitae's next GEN germline mutations and testing. (Advanced metastatic hormone sensitive prostate cancer) The results came back positive for two germline mutations:

RET and BRCA2. Both mutations were described as having "unknown significance" and we were told that neither were pathological mutations. Well… We know for sure that BRCA2 is definitely a pathological mutation and we understand the implications of that(DDR mutation, heterogeneous cancer, much more aggressive disease, eligible for PARP inhibitors) . My question is: why do they consider BRCA2 to be of unknown significance and what is the significance of RET Germline mutation for advanced prostate cancer? Does germline RET mutation predispose cancer cells to NEPC transition?

[Tall_Allen]

Where did you hear that germline RET mutation predisposes cancer cells to NEPC? Not all BRCA2 mutations are alike- it depends which BRCA2 mutation it is.

[Farmhand in reply to Tall_Allen]

I was only guessing about the RET mutation… Comparing it to RET mutation and MEN2 ...hopefully I am wrong and there is no significance?I will read the report more closely for details of BRCA2. Are there particular details that I should be looking for as to that type of BRCA2?

[Farmhand in reply to Farmhand]

The above screenshot is a copy of the test results. Our oncologist interpreted the BRCA2 mutation as a legitimate pathological mutation as several family members have breast cancer.

Invitae germline mutation test results

[Tall_Allen in reply to Farmhand]

As I suspected, you have mutations in BRCA2 that have not been implicated in cancer.