I am new to the site and have spent many days reading through the volumes of significantly helpful member posts and questions, as well as the articles which provide direct links to abstract articles.
I am trying to understand what it means when someone "reports" that they have "normal cytogenetics".
Is this even possible in multiple myeloma or for that matter in the pre-state diseases of MGUS and SMM?
What I have come to understand about the multiple myeloma clone process is this -- in order to even "start" the monoclonal plasma cell process, a cell must undergo an "abnormal" change. So how is it even possible for someone to say they have "normal cytogenetics"?
I thank everyone who is willing to try to explain this phenomenon to me which has casued me enormous confusion with what I understand to date.
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7 posts
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Re: Normal cytogenetics - what does it mean & is it possible
In my last FISH test which I believe is a type of cytogenetic test my results came back normal too. But I know that they did not test for every known abnormal chromosomal change that is known to cause myeloma, only a subset of selected known chromosomal defects that are associated with myeloma that are “high risk” or known to be difficult to treat were tested for in my case and I believe this is the same for most people when they get this kind of testing done. I do not know if it is possible that myeloma could be present with no DNA or chromosonal problems. It may just be that the defect has not been recgonized or discovered yet.
If someone is enrolled in a clinical trial they may get a more complete cytogenetic test to support the trial objectives. And I believe the Multiple Myeloma Research Foundation (MMRF) CoMMpass study is doing analysis on recording the entire genome for patients who are enrolled in that study, which are only those who have not yet started treatment. The CoMMpass study is a big myeloma research trial with 1000 patients that will track what genetic defects these patients had and how they responded to the treatments they received. A great deal about what treatments work best for specific types of chromosomal defects may be learned from this study.
If someone is enrolled in a clinical trial they may get a more complete cytogenetic test to support the trial objectives. And I believe the Multiple Myeloma Research Foundation (MMRF) CoMMpass study is doing analysis on recording the entire genome for patients who are enrolled in that study, which are only those who have not yet started treatment. The CoMMpass study is a big myeloma research trial with 1000 patients that will track what genetic defects these patients had and how they responded to the treatments they received. A great deal about what treatments work best for specific types of chromosomal defects may be learned from this study.
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
Re: Normal cytogenetics - what does it mean & is it possible
Hello from Seattle,
There are two types of genetic testing that are routinely used in multiple myeloma. One is sometimes referred to as "conventional" cytogenetics or "metaphase" cytogenetics. This was the only way we could analyze chromosomes and genes for along time. This type of analysis really only detects major problems in genetic struction. Single gene mutations cannot be seen. With conventional cytogenetics you can actually see the chromosomes using a microscope. But only major changes in a chromosome structure are detectable. It is common to have a "normal" cytogenetic report by conventional cytogenetics.
With FISH you can test at the singe gene level and it is therefore much more sensitive. Changes that are completely invisible with conventional cytogenetics are detectable with FISH. You generally only look at one or two genes at a time with FISH. It is less common to have completely normal FISH results, For instance, FISH often picks up the del13 mutation. This is not an adverse finding but it is very common in myeloma patients by FISH.
You are correct that a "normal" report by conventional cytogenetics does not mean you have a normal genome. Almost all myeloma patients have genetics changes if one looks at every gene. For now though these two types of testing are the only ones readily available and affordable.
There are two types of genetic testing that are routinely used in multiple myeloma. One is sometimes referred to as "conventional" cytogenetics or "metaphase" cytogenetics. This was the only way we could analyze chromosomes and genes for along time. This type of analysis really only detects major problems in genetic struction. Single gene mutations cannot be seen. With conventional cytogenetics you can actually see the chromosomes using a microscope. But only major changes in a chromosome structure are detectable. It is common to have a "normal" cytogenetic report by conventional cytogenetics.
With FISH you can test at the singe gene level and it is therefore much more sensitive. Changes that are completely invisible with conventional cytogenetics are detectable with FISH. You generally only look at one or two genes at a time with FISH. It is less common to have completely normal FISH results, For instance, FISH often picks up the del13 mutation. This is not an adverse finding but it is very common in myeloma patients by FISH.
You are correct that a "normal" report by conventional cytogenetics does not mean you have a normal genome. Almost all myeloma patients have genetics changes if one looks at every gene. For now though these two types of testing are the only ones readily available and affordable.
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Dr. Edward Libby - Name: Edward Libby, M.D.
Beacon Medical Advisor
Re: Normal cytogenetics - what does it mean & is it possible
Hi Anonymous, Thanks for asking this question!
Thanks Dr. Libby for providing this explanation. You state "It is less common to have completely normal FISH results ...".
Would a normal FISH result be more common in those with MGUS or Smoldering multiple myeloma ? Or is FISH sensitive enough to detect the single gene level abnormalities even in the earlier stages in the disease, especially the initiating trisomes and IGH translocation events.
Best regards,
Dana H
Thanks Dr. Libby for providing this explanation. You state "It is less common to have completely normal FISH results ...".
Would a normal FISH result be more common in those with MGUS or Smoldering multiple myeloma ? Or is FISH sensitive enough to detect the single gene level abnormalities even in the earlier stages in the disease, especially the initiating trisomes and IGH translocation events.
Best regards,
Dana H
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Normal cytogenetics - what does it mean & is it possible
Normal FISH testing is probably more common in asymptomatic myeloma and MGUS.
The FISH test only looks for a very limited number of genetic changes and so there are many many genetic changes that current FISH testing is not designed to detect. FISH does look for those changes that we know the most about and those that clearly affect prognosis..
The FISH test only looks for a very limited number of genetic changes and so there are many many genetic changes that current FISH testing is not designed to detect. FISH does look for those changes that we know the most about and those that clearly affect prognosis..
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Dr. Edward Libby - Name: Edward Libby, M.D.
Beacon Medical Advisor
Re: Normal cytogenetics - what does it mean & is it possible
Hi Dr. Libby,
Thanks so much for responding and clarifying.
Best regards,
Dana H.
Thanks so much for responding and clarifying.
Best regards,
Dana H.
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Normal cytogenetics - what does it mean & is it possible
I, too, am trying to understand the cellular level of myeloma and the genetics involved. From what I have learned, stem cells in the bone marrow differentiate into B cells that mature into plasma cells that produce the antibodies. Where along the pathway does the genetic mutation occur? Do the B cells become abnormal during their creation (and thus mature into abnormal cells) or do normal B cells begin to mature into normal plasma cells that are then affected (as they divide) by a yet-unidentified genetic mutation? I currently have normal cytogenetics, so there must be some other undiscovered instigator. Will they ever discover this factor?
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gardengirl - Name: gardengirl
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Nov. 2013
- Age at diagnosis: 47
7 posts
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