Help me interpret this

Options
Anonymous
Anonymous Member Posts: 1,376

This is from my path report from my brain mets, which were surgically removed three weeks ago.

"A TP53 variant, E154V, was detected. TP53 is a tumor suppressor gene. Germline variants of TP53 have been associated with Li Fraumeni syndrome."

My tumor also tested positive for PIK3CA variant, so I was more focused on that and didn't see the stuff about TP53 until now.

I was Dx'ed with Stage III triple positive at 28 and with brain mets at 30. I have a family history of cancer, mostly breast, but I'm the only one on both sides to have cancer before 50. Because of that, I never considered the possibility of Li Fraumeni. I'm in shock

Comments

  • Mamiya
    Mamiya Member Posts: 432
    edited February 2016

    I thought the TP53 in the tumor (somatic) was different than the TP53 DNA mutation (germline) associated with Li Fraumeni. I am not totally sure how this works but I was tested and had no detectable genetic mutations of my DNA RE: TP53 but my tumor has TP53 and I am told that is fairly common... Following for some more info from people who know more about this than we do ;)

  • Anonymous
    Anonymous Member Posts: 1,376
    edited February 2016

    Wait, the report said something else.

    "TP53 is a tumor suppressor gene. Germline variants of TP53 have been associated with Li Fraumeni syndrome. Somatic TP53 variants are frequently seem in different malignancies."

    So it doesn't differentiate???

  • ShetlandPony
    ShetlandPony Member Posts: 4,924
    edited February 2016

    The question is this: If there is a TP53 variant in a tumor (somatic), could that variant be either just in the tumor OR in all the person's DNA (germline)? I think it could be either case, and they would have to check your DNA to know. But I'm not sure! I asked my onc this type of question because of some stuff on my Foundation One test, but I have not had an answer yet. If you post under a thread with genetics in the title, maybe more knowledgeable members would notice and comment?

    I'm so sorry you have to deal with this.

  • Anonymous
    Anonymous Member Posts: 1,376
    edited February 2016

    I did a search of TP53 on this site and I found this in a different post.

    "t is important to keep in mind that a mutation is the p53 gene is not considered to be inherited like the BRCA gene (in other words, it isn't what we call an inherited mutation, but instead a somatic mutation) p53 genes will mutate over our lifetime due to environmental stressors. So we probably all have a mutated p53 gene in the cells that turned into breast cancer.

    Testing for that mutation does not mean your children may have it. It means we smoked, got exposed to carcinogens, ate too much junk food, hung out in a large city with smog, etc. That's why looking for the antibodies to a mutant p53 protein isn't that informative. Where my company is doing the research is looking at it as a cancer screen. It is mutated in so many cancers.

    Does that make sense? I can try to explain it better, but please don't think it is a test like BRCA 1 and 2, because it is definitely not. In other words, you have a mutation because of what you have done, where you have been, how you have lived. If your child is living differently, they likely won't get the mutation. This is why it isn't useful in genetic testing for a predisposition to BC or ovarian cancer like BRCA, but why it is a good screen for an existing cancer."

    So does that mean if I don't have the genetic version that I did this to myself? Effed upso badly it was more likely to be treatment resistant? How did I do so much damage in only 28 years on this earth? I'm an athlete, never smoked, never did drugs, never drank heavily, maintain a sub 25 BMI for all but one year. But 1) I really like chocolate 2) the summer I was 20 I worked 12 hour days and didn't know how to cook so I ate fast food every day, I didn't think it would do me any harm because I was thin and had an active job 3) I didn't know anything about bpa and used to heat stuff in cheap plastic all the time and drank out of plastic water bottles.

    Ugh this sucks. Either I have a mutation that will dispose my family members to scary, early onset cancers or I have a mutation that makes me resistant to treatment (which surprises me because I did neo chemo and had an incomplete but still strong response - cleaned out a bunch of my lymph nodes and shrank the tumor hugely).

  • Mamiya
    Mamiya Member Posts: 432
    edited February 2016

    Bad, when I had my guardant circulating tumor cells testing and it showed the same thing you are seeing on your report I posted it up on another group I am a member of and got feedback from a bunch of people who had the same thing and went on to get treatment and are well 4,5, and 8 years later so I wouldn't worry SO much about it. My own has proven to be chemo resistant but we don't know that is all from the TP53.

  • Anonymous
    Anonymous Member Posts: 1,376
    edited February 2016

    Alright, I found out something else interesting.

    TP53 also seems to be related to CHEK2 mutation. CHEK2 is also related to colon and prostate cancers, which have been present in my family.

    So there seems to be three possibilities with the TP53 mutation.

    1) I have it but there's no link to hereditary cancer - kinda weird since I had a good response to neo chemo.

    2) I have it and Li Fraumeni.

    3) I have it and CHEK2.

    Of course there's Door #4 - I have a germline mutation that hasn't been identified yet.

    I really need to speak to a genetic counselor

  • Anonymous
    Anonymous Member Posts: 1,376
    edited February 2016

    My family hx is as follows.

    Maternal Great grandma - colon cancer at 69

    Paternal grandmother - breast cancer at 61

    Maternal great aunt - breast cancer at 58

    Mother - breast cancer (ER/PR+ and her2-) at 64

    Paternal uncle - prostate cancer at 54

    Maternal aunt - no cancer but colon polyps found at 57

    So def a family history, but no young cancer besides me


  • ShetlandPony
    ShetlandPony Member Posts: 4,924
    edited February 2016

    Can you make an appointment to consult with a cancer genetics expert at a major cancer center? In two appointments they will take a history,make a pedigree chart, test as appropriate, interpret your tests, give advice for you and your relatives, and answer your questions. And please remember what this expert said to me as he leaned in with his face next to mine: It's not your fault.

  • elabee
    elabee Member Posts: 20
    edited March 2016

    Hi Bad_At_Usernames,

    As someone with Li-Fraumeni syndrome, here's a quick overview of my experience.

    I worked with the genetics counselor at my hospital. Initially, my genetics counselor and team thought it was likely I would have the BRCA mutation. If the BRCA came back negative then I would be tested for the tp53 germline mutation.

    Some additional info: I was diagnosed with breast cancer at 34 (should've been when I was 33, but I was misdiagnosed). Being under the age of 35, triple positive and negative for BRCA is what prompted my team to have me tested for the germline mutation of TP53.

    As you mentioned there is a distinction between a germline tp53 mutation and tp53 mutations that occur in tumors. The germline mutation is often times inherited. Although, it's thought that 20% of folks with the germline mutation are de novo (my twin and I are de novo).

    With a germline mutation, you have the mutation in all the cells of your body not just where your tumor originated. Although there are rare cases of folks who have a mosaic germline mutation where the mutation only occurs in parts of their body.

    Regardless, all folks who have a germline mutation have a 50-50 chance of passing it on to their offspring. Folks who have a tp53 mutation as part of their tumor do not have that risk of passing it on.

    I know that's a lot of information, but I hope it was helpful.

  • Kelhab
    Kelhab Member Posts: 11
    edited September 2021

    hi how are you. Can you pls help me here… i just found out that i have p53 mutation. I cant understand how and i have kids to think about i cant function.

Categories