Confusion on two different results

KBL

I had blood drawn last year and had genetic testing for a number of different genes. All came back negative. I then had a bone biopsy last month, and I've been asking to be tested for the PIK3CA gene. Unfortunately, after three different specimens were sent, they didn't have enough to test. I got a report back that had a bunch of different things on it, but it had that the AR, MLH1, MSH2, MHS6, PMS2, and PTEN were positive. Why would it say negative on one result and positive on another? One of them is wrong. Now I'm totally confused.

moth

There can be a difference between YOUR genetic code and the tumor's. Mutations acquired by a tumor are called somatic whereas errors in a person's DNA are germline mutations. Does that help?

ShetlandPony

KBL, part of the confusion could be about genomic testing of a tumor sample or your blood for circulating tumor cells (looking for somatic mutations) vs. genetic testing of you for inheritable genetic mutations (Looking for germline mutations). Can you tell us the names of the tests you have had done, and when, and on what tissue or blood?

It sounds like in the first instance they did a blood test and looked for inheritable genetic mutations like BRCA Mutation etc. that can predispose a person for cancer, and did not find any mutations in the ones they checked. Is that right? For this sort of test, it is important to know what genes they looked at. Everyone has the genes, but the question is, do yours have any harmful mutations (changes from the usual).

It sounds like in the second case they took a sample from a bone met and wanted to see if it had a targetable mutation (There is a drug to treat it) like one in PIK3CA, but were unable to run the test because the sample was too small?

In the third case, it is hard for me to guess. AR could be androgen receptor; if positive the tumor has androgen receptors. But the other genes you name are typically on cancer panels that test the blood for inherited cancer-causing genetic mutations. The first four are Lynch genes; it would be surprising to have mutations in all of them. Be careful to distinguish between "we looked at this gene" vs. "this gene had a mutation". To further confuse matters, a germline mutation is in all the cells of the body, so will show up in a cancerous cell as well.

If you want to PM me a copy or post here with no personal info I might be able to clarify things and suggest what to ask your oncologist or genetic counselor. I have had both kinds of testing done and got useful info from both.

Edit: Apparently typing while moth was posting!

KBL

Wow, great information Moth and ShetlandPony. I am actually understanding what you’re saying. You got it absolutely right, ShetlandPony. I had the blood tests, which were negative and then had the bone met tested, which said those things were positive. The main reason I want to know is to make sure whether my daughter should be genetically tested by blood. If they weren’t in my blood, does she still have a chance to have those genes? Thank you both so much.

moth

So just for precision, everyone HAS those genes. We all have the BRCA genes for example (they're actually tumor suppression genes). The issue is whether they're normal or mutated.

I *think* that if your DNA don't show germline mutations then offspring does not need testing. I had testing done through color genomics in 2018 and came back negative and was told my dd would just need to start mammograms earlier & they recommended not using hormonal birth control.

When I had the genetic test done, there was a genetics counsellor who sent the letter to me and left her # to call with with questions. I wonder if you have that from your tests? Because they would be best at advising re implications for offspring.

ShetlandPony

A cancer genetics counselor (not a PCP, breast surgeon, or even oncologist) is indeed the person to advise you on whether you or family members need testing, and what particular tests to do. Large cancer centers will have a genetics department with the right people to see. They will help you make a family tree showing all cancers, not just breast, since some mutations predispose to more than one kind of cancer.

Can you tell me the name of the test done on your tumor sample? Was it perhaps Foundation One, Guardant, or Tempus? I am a bit baffled by your statement that “they didn't have enough to test. I got a report back that had a bunch of different things on it, but it had that the AR, MLH1, MSH2, MHS6, PMS2, and PTEN were positive.“ How could there be these results if there wasn’t enough to test PIK3CA? And it would be surprising to have all four of those Lynch genes mutated. Normally a report will not say “positive” or “negative” for such genes. It will say “alteration detected” or “Pathological variant” or “variant of uncertain significance”. I really want to clarify this because if your tumor sample had these genes mutated, it would be important to do germline genetic testing on your blood, since these mutations are not common as somatic (tumor only) mutations but are more often germline (inherited). Again, I suspect there is an interpretation difficulty here. So not to panic.

I know this because when my tumor sample showed an MSH6 mutation, it alerted me and family members to get genetic testing. Four of seven of us Tested have an inherited MSH6 mutation, as well as (Presumed) a relative who had colon cancer, and two of us With the mutation have had ILC. All require extra screening for breast, colon, endometrial, and skin cancer.

KBL

Thank you again, Moth and ShetlandPony. For full disclosure, I haven’t talked to my doctor yet about these results. Once I do, I’ll let you know what they say. Shetland, I’ll try to send you a private message with the report. I’d rather not put it here. As you can see, I don’t know the first thing about this stuff.

ShetlandPony

Oh, I am glad you will be talking to your doctor about your test results. I think it will be so much easier for you to understand the test results with an in-person discussion and the report in front of you both. Hopefully our discussion has helped you prepare for that appointment. Let us know what you find out. I’d be happy to look at your report and give you comments or questions to take to your doctor.

KBL

Thank you, ShetlandPony. I really appreciate any help. I sent you a private message, and I took a picture of the portion I was talking about and will send it to you now. The report itself is ten pages, and I can send the whole report to you when I return home on Saturday.

ShetlandPony

Oh, ok, it is all making sense now. I see that, as you said, this was all IHC to determine levels of various protein expression on the cells, which could possibly help guide treatment. (Learned something new. I did not know there were IHC tests for all those markers.) This test does not look for mutations in the cancer cells. So as far as I know, it does not mean anything about mutations that could be inherited, or genetic testing of relatives. No alarms there.

It sounds like you are interested in finding out if the cancer has a PIK3CA mutation so that Piqray would be a treatment option. And it sounds like the biopsy only got enough material to run the IHC but not the genomic testing needed to answer this question. In cases where the biopsy does not get enough for genomic testing, a liquid biopsy to look for circulating tumor cells in the blood may be tried instead, so maybe your oncologist will consider that.

KBL

Yes, I’m trying to see if I have the PIK3CA for Piqray. My doc told me last time if there still wasn’t enough, we would do a liquid biopsy, so I’m sure that’s next. Thank you so much for taking the time to help me understand

SeeQ

KBL, Your timing with this question is spot on. At my last MO appt (and first with my new MO), he was talking about getting Foundation One testing, and I really didn't understand what that was, and what was the benefit. This discussion helps. My MO thought BMDA (in FL) may have done the test - he was going to check, but I'm pretty sure they didn't.

So, here's a funny logisitics question for those who have used MDA for a second opinion. I know they received the original biopsy 'cassettes' for their own lab to analyze; do they automatically send them back to the place that did the biopsy? (That seems logical.)

And *I think* the IR said something about getting plenty of sample material, and my MO said something about having needing to have enough for the F1. How many times is it likely that the same biopsy material can be used? I'm trying not to borrow trouble, but the question keeps rolling around in my head. I wish I'd paid more attention to exactly what the IR said, but my de novo diagnosis came from that biopsy; I had no idea what I was headed into at that time.

Edit -- I just occurred to me that I should have specified liver biopsy.