I let out a big sigh of relief when my cytogenetics [chromosomal abnormalities] came back negative. However, when I asked the myeloma specialist if that can change, he said "yes".
Does disease progression cause the change or does the change cause the disease to progress? (the chicken or the egg?)
Forums
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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
Re: Can cytogenetics (chromosomal abnormalities) change?
Here is a link to some recent research that describes how myeloma evolves over time.
Melchor, L, et al, "Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma," Leukemia, Jan 13, 2014 (abstract)
Abstract:
Although intratumor heterogeneity has been inferred in multiple myeloma (multiple myeloma), little is known about its subclonal phylogeny. To describe such phylogenetic trees in a series of patients with multiple myeloma, we perform whole-exome sequencing and single-cell genetic analysis. Our results demonstrate that at presentation myeloma is composed of two to six different major clones, which are related by linear and branching phylogenies. Remarkably, the earliest myeloma-initiating clones, some of which only had the initiating t(11;14), were still present at low frequencies at the time of diagnosis. For the first time in myeloma, we demonstrate parallel evolution whereby two independent clones activate the RAS/MAPK pathway through RAS mutations and give rise subsequently to distinct subclonal lineages. We also report the co-occurrence of RAS and interferon regulatory factor 4 (IRF4) p.K123R mutations in 4% of myeloma patients. Lastly, we describe the fluctuations of myeloma subclonal architecture in a patient analyzed at presentation and relapse and in NOD/SCID-IL2Rγnull xenografts, revealing clonal extinction and the emergence of new clones that acquire additional mutations. This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment. We conclude that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in myeloma.
Melchor, L, et al, "Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma," Leukemia, Jan 13, 2014 (abstract)
Abstract:
Although intratumor heterogeneity has been inferred in multiple myeloma (multiple myeloma), little is known about its subclonal phylogeny. To describe such phylogenetic trees in a series of patients with multiple myeloma, we perform whole-exome sequencing and single-cell genetic analysis. Our results demonstrate that at presentation myeloma is composed of two to six different major clones, which are related by linear and branching phylogenies. Remarkably, the earliest myeloma-initiating clones, some of which only had the initiating t(11;14), were still present at low frequencies at the time of diagnosis. For the first time in myeloma, we demonstrate parallel evolution whereby two independent clones activate the RAS/MAPK pathway through RAS mutations and give rise subsequently to distinct subclonal lineages. We also report the co-occurrence of RAS and interferon regulatory factor 4 (IRF4) p.K123R mutations in 4% of myeloma patients. Lastly, we describe the fluctuations of myeloma subclonal architecture in a patient analyzed at presentation and relapse and in NOD/SCID-IL2Rγnull xenografts, revealing clonal extinction and the emergence of new clones that acquire additional mutations. This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment. We conclude that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in myeloma.
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Mark
Re: Can cytogenetics (chromosomal abnormalities) change?
The links didn't help me to understand anything. Maybe if I were to read it over several times when not tired. It was very confusing to me.
I am curious to know if the cytogenics can change for the better. I have the t 4:14 issue. Can this change?
I am curious to know if the cytogenics can change for the better. I have the t 4:14 issue. Can this change?
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kjpoppit - Name: Kim Nelson
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Sept. 19th, 2013
- Age at diagnosis: 47
Re: Can cytogenetics (chromosomal abnormalities) change?
Your cytogenetics (metaphase cytogenetics and FISH) can evolve throughout therapy. I have a number of patients who have had significant changes in their molecular profile as they go through therapy. We think about an increasing number of copies of chromosome 1q and deletion of 17p as evidence of a more aggressive relapse.
How these changes occur are likely the result of at least two things:
For those who are particularly interested in this topic, here are some references with additional information:
Bolli et al,"Heterogeneity of genomic evolution and mutational profiles in multiple myeloma," Nature Communications, 2013 (full text of article)
Lohr et al, "Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy," Cancer Cell, 2014 (full text of article)
Morgan et al, "The genetic architecture of multiple myeloma," Nature Reviews Cancer, 2012 (abstract)
How these changes occur are likely the result of at least two things:
- The existence of small subclones, or populations of myeloma cells, that are selected with therapy, and
- The acquisition of new changes in the presence of the selective pressures of therapy.
For those who are particularly interested in this topic, here are some references with additional information:
Bolli et al,"Heterogeneity of genomic evolution and mutational profiles in multiple myeloma," Nature Communications, 2013 (full text of article)
Lohr et al, "Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy," Cancer Cell, 2014 (full text of article)
Morgan et al, "The genetic architecture of multiple myeloma," Nature Reviews Cancer, 2012 (abstract)
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Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Can cytogenetics (chromosomal abnormalities) change?
I was told when I was diagnosed 1/12 that there was a cytogenetic factor involved in my multiple myeloma. But I have no idea what FISH or flow cytometry are? Can you enlighten me, provide a link or suggest questions I might ask my team of doctors? Thanks
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1World - When were you/they diagnosed?: 1/4/2012
- Age at diagnosis: 59
Re: Can cytogenetics (chromosomal abnormalities) change?
The first thing I would ask your doctors is for copies of your labwork to include flow cytometry, cytogenetics and FISH analysis. That way you can study them at home (with internet references) to get a better understanding.
Flow cytometry determines if there are abnormal cells in the bone marrow.
Cytogenetics evaluates the chromosomes (DNA) in normal and abnormal cells (can look for translocations or deletions).
FISH (fluorescent in situ hybridization) is similar to cytogenetics and uses dyes that attach to specific parts of chromosomes to highlight changes or abnormalities (there are specific chromosomes commonly involved in numerical or structural anomalies in myeloma).
If you have copies of your labs, you will be able to tell which factors are involved.
Hope this helps! Perhaps someone can find you links (I'm not very good at that!)
Flow cytometry determines if there are abnormal cells in the bone marrow.
Cytogenetics evaluates the chromosomes (DNA) in normal and abnormal cells (can look for translocations or deletions).
FISH (fluorescent in situ hybridization) is similar to cytogenetics and uses dyes that attach to specific parts of chromosomes to highlight changes or abnormalities (there are specific chromosomes commonly involved in numerical or structural anomalies in myeloma).
If you have copies of your labs, you will be able to tell which factors are involved.
Hope this helps! Perhaps someone can find you links (I'm not very good at that!)
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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
Re: Can cytogenetics (chromosomal abnormalities) change?
Thanks, Karen. That does help. I see Dr tomorrow for labs and Zometa. I will ask about it. I can see my labs on line. Maybe it's been there and I just haven't known what to look for. But I will certainly ask tomorrow.
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1World - When were you/they diagnosed?: 1/4/2012
- Age at diagnosis: 59
Re: Can cytogenetics (chromosomal abnormalities) change?
If you know for sure you already have myeloma based on other test, I do not believe that you would necessarily need to do a flow cytometry test. It is my understanding that flow cytometry is a very sensitive test that is used to detect extremely low levels of myeloma cells. It is often done to check for residual disease when other less sensitive test show no signs of myeloma. If you already have other less sensitive lab test results that indicate myeloma is present, flow cytometry is just going to tell you something you already know, you have myeloma cells. I am not a doctor though so I would always recommend discussing all tests and treatments with you oncologist.
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
Re: Can cytogenetics (chromosomal abnormalities) change?
When I was diagnosed my oncologist told me that the chromosomal abnormalities are only in the cancer cells; therefore, the abnormalities can definitely change with treatment. She said FISH tests can change in that you can see some abnormalities go away, while you might see new abnormalities appear? I'm hearing such mixed messages on this, can anyone clarify or expand upon that? Thank you!
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Lizzie - Name: Lizzie
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: Jan 2014
- Age at diagnosis: 43
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