Has anyone had their genetic testing change over time?

[paige20180]

My husband tested PTEN loss in his first genetic tests when tissue was taken from his RP in mid 2017. We recently had new genetic testing performed with Biocept. Circulating cancer cells were found in his blood (30) however, no PTEN mutation was found. I want to jump for joy but my research does not support PTEN going away. I read you are born with the gene and there is no cure to repair chromosome 10. Any thoughts? Thanks!

[Tall_Allen]

You are confusing germline and somatic mutations. Germline are the kind you are born with and don't change. Such testing is often done now with saliva.

Tissue tests and blood tests of circulating tumor cells are looking for somatic mutations - changes in tumor cells. Tumor cells do evolve, so that earlier tumors may have different genomic profiles from later tumors. Also, circulating tumor cells are highly dependent on tissue conditions. Some tests look at cell-free DNA - which is not as dependent upon the cells remaining intact.

[paige20180 in reply to Tall_Allen]

Can’t thank you enough for your expertise. Would you mind explaining TA, why there would be a test for a change in PTEN? In fact, why would this test for somatic changes be of any value? If we had not had the first test and only the second, we could be led to believe he did not have a PTEN mutation and may not make the best treatment choices. Why wud they look for a change in certain genes if they are Germline? Thanks so much for your time educating me.should I be happy no further changes or new mutations were found after 28 months?

[Tall_Allen in reply to paige20180]

From what you've written, they aren't germline - they're somatic. You didn't mention any germline tests. PTEN loss is a common somatic genomic alteration for which there aren't any current treatments.

[paige20180 in reply to Tall_Allen]

I am obviously have lots of research to do. I thought PTEN was something you were born with. You got it from mom and Dad. Your kids have a 50% chance of inheriting. So I guess that's why its hard for me to understand how a mutation you are born with could be somatic. So I assumed when Foundation One tested the actual pathology tissue, this was a genomic alteration. The second test was blood. I thought PTEN was not something that could "change" but was something you were born with or not. No changing. Thanks a lot for enlightening me. I'll at least ask much better questions when we speak to the genetic counselor. thanks again! Soit makes sense that two tests, both somatic would have different results?

[Tall_Allen in reply to paige20180]

No. PTEN loss is a genomic aberration that is common in tumors. The blood test was a CTC test, not a germline test. Tumors may have different genomic characteristics depending upon when they occurred.

[paige20180 in reply to Tall_Allen]

I’ve read a lot about PTEN. I think I understand a lot about it. The first test that detected PTEN tested the prostate tissue from his RP. I did not know this was a somatic test but thought it was a germline.

I understand cancer mutates. That’s why he was retested. I just didn’t expect to be PTEN positive then negative since as cancer progressed. I was hoping there was a mistake and he didn’t have the mutation.

It’s scary to me you could be tested. Maybe it’s your first genetic test and like my husband, it tells you you have no mutations but you actually do.

[Tall_Allen in reply to paige20180]

Maybe I didn't make clear that the genomic alteration that is correlated with a tumor's aggressiveness is PTEN loss. So tumors go from being PTEN positive to PTEN negative as they undergo genomic breakdown.

[paige20180 in reply to Tall_Allen]

You have done a great job explaining. It’s just I knew nothing 2 days ago and with your help I know so much more. You helped point me the right direction. It’s hard to explain in writing but I’m thankful for you. I feel empowered trying to understand this to help my husband.

[Dd7757 in reply to Tall_Allen]

The confusion seems to be around the tissue biopsied after the RP. Paige was under the belief that if the PTEN loss was detected in the prostate tissue that it was a germline mutation, She further believed that if it did not show up in the CTC ‘s there may have been a mistake in the biopsy. You are saying the presence of PTEN loss in the prostate tissue is not an indication it is Germline but is an indication it is somatic...that is the mutation occurred as the prostate tumor was developing. You further say a saliva test can reveal whether one has a germline PTEN mutation . Do you suggest that a saliva test be performed or do you feel ascertaining germline existence is now clinically irrelevant ?

Thanks for all your wisdom so generously given.

[Tall_Allen in reply to Dd7757]

PTEN loss is almost always found in PC somatic mutations, almost never in germline. Paige wasn't clear about whether it is PTEN loss that was found. PTEN is a tumor-suppressor gene, so its loss (=negative for PTEN), and not a positive for PTEN finding, is a risk factor. Either way, there is really no actionable implication.

[paige20180 in reply to Tall_Allen]

Thanks Tall_allen. Brilliant. Not the best news but information is power. Got it.

[paige20180 in reply to Dd7757]

That is exactly what I was wondering! Well done. Thanks to Charles and the great videos he posted, I understand somatic and germline I believe at a 5th grade level lol. so you have two strands of DNA. Maybe one mutation is a germline from parents. But your second copy may keep that unfortunate mutation at bay. But An embryo could form a somatic mutation. Fascinating these mutations could form as an embryo develops. A somatic mutation focuses on one area. A tumor. Not throughout the body. But cancer doesn’t develop until the second copy of dna is damaged somehow (somatic). So my husbands first genomic test looked at a prostate tumor which had PTEN loss. A somatic change specific to this tumor. Not necessarily a germline mutation.

27 months later he has a blood test with CTC of 30. (I pray some dead since he had radiation on two metastasis 10 days before.) But this test had no PTEN loss or any mutations. So I’m starting to comprehend the PTEN loss is specific to that one tumor.

I was thinking my husband was born with a germline PTEN loss mutation. But it looks as though something in his environment caused the chromosomal defect to allow cancer to grow? Two dna mutations? Maybe one germline and one somatic. ( all the flights over the North Pole, radar on, circadian rhythms out of wack?)

So I was thinking my husband was born with a genetic defect that allowed tumors to grow unchecked like in Harmatoma Syndrome. Now I understand somatic ( I think)

So yes. Is it worth testing for a germline mutation? I’d it any better to have a somatic mutation and that tumor is now dead.? And my husbands blood shows no evidence of PTEN loss or once you have a tumor with PTEN loss, does that mean this is likely to continue so it doesn’t matter if it’s a germline or somatic mutation... the result is the same?

Thankful for the education you guys!

[ctarleton]

You might find these videos from this year's UCSF 2019 Patient Conference on Prostate Cancer helpful in gathering one's thoughts and questions before meetings with doctors about Genetics or Systemic treatment options for advanced prostate cancer.

Genetics 101

uctv.tv/shows/Prostate-Canc...

Systemic treatments:

uctv.tv/shows/Systemic-Ther...

Charles

[paige20180 in reply to ctarleton]

Thanks so much! I'll take all the help I can get trying to help my husband I adore.

[j-o-h-n in reply to paige20180]

And I'm sure he adores you....(you're wonderful)

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 09/17/2019 8:13 PM DST

[paige20180 in reply to ctarleton]

Charles. These videos were spot on and fascinating. Thanks to both of you!!!

[Balsam01 in reply to ctarleton]

These videos are excellent!