Chromosome Information?

[Darice]

I guess I just keep trying to learn more about this darned MDS, but I wondered whether anyone has found something like "Chromosomes for Dummies" that can help me to understand all the chromosome stuff without getting incredibly technical? I want to better understand what's going on and would welcome any articles people have found explaining all of this better.
Thanks

[mausmish]

Cytogenetics from my personal experience:

I was extremely confused when I received my first cytogenetic report. I understood that I had "complex cytogenetics" meaning multiple chromosome abnormalities and that this was very bad news. After a lot of reading, this is my basic understanding of the notations in the report. Notations vary slightly from lab to lab. Anyone, please correct me if I'm wrong about any of this info. I have no medical expertise and don't want to give out misinformation.

Cytogenetics, for our purposes, is the study of chromosomes and their structure. We are not talking about inheritance and genetics. Each of our cells has 23 pairs of chromosomes or a total of 46. The term "karyotype" means the arrangement and structure of the chromosomes. If one has no chromosome abnormalities, it will be designated 46,XX for a female or 46,XY for a male.

The pairs of chromosomes are labeled 1 through 23, and each individual chromosome has two arms, the top or short arm is labeled "p" and and the bottom or long arm is labeled "q". Each arm has numerically labeled regions.

In damaged chromosomes, anomalies or defects are generally classified as deletions, additions, translocations or inversions.

Deletions:If an entire chromosome is missing, it is designated monosomy, such as "monosomy 7" or "-7"; If only part of a chromosome is missing it is designated del( ). For example a deletion of the entire q arm of chromosome 5 might be notated "del(5q)" or "-5q"; if only part of an arm is missing, there will be an additional notation showing which region, for example "del(5q21:33)" or "del(5)(q21)".

Additions: Sometimes there is an extra copy of a chromosome, called trisomy, such as "trisomy 8" or "tri(8)" or "+8". Sometimes instead of a copy, there is an addition of unknown origin, designated "marker" such as "mar(unknown)" or "+mar".

Inversions: Sometimes the arms of a chromosome are partially or completely inverted - all or part of the p arm is swapped with all or part of the q arm on the same chromosome. This is noted something like "inv(4)(p13q22)" to show which regions are swapped.

Translocations: Sometimes part of a chromosome gets swapped with or added to part of a different chromosome. This is noted something like "t(9;22)(q34;q11.2)" meaning part of chromosome 9 (region q34) is swapped with part of chromosome 22 (region q11.2).

Going back to my own report as a full example, here is what it showed:

46,XX,-3,del(5)(q14q33),-6,+8,+mar[14]/46,XX[6]

My sample size was 20 cells. Of these [14] were abnormal with multiple anomalies and [6] had no defects.

46,XX = each cell had 46 chromosomes, all female

-3 = monosomy 3 = one of the chromosomes in pair number 3 was completely missing

del(5)(q14q33) = region 14-33 of the long arm q of one of my chromosomes in pair number 5 was deleted. This is common in MDS. If it had been the only anomaly, my prognosis would have been good but combined with my other anomalies, it wasn't.

-6 = monosomy 6 = one of the chromosomes in pair number 6 was completely missing

+8 = trisomy 8 = I had an extra copy of one of the chromosomes in pair number 8. This may be associated with AML.

+mar = I had some extra chromosome material of unknown type and origin. Sometimes the material can be identified and offers clues to prognosis or origin. Mine did not.

After 3 cycles of Vidaza, I had the same abnormalities but only in 1 of the 20 cells sampled in my biopsy, so the report looked like this:
46,XX,-3,del(5)(q14q33),-6,+8,+mar[1]/46,XX[19]

I'm happy to say that I've had 4 bone marrow biopsies since November 2010, all with cytogenetics reported as 46,XX[20], i.e. no abnormalities.

Hope this is of some use to you!

p.s. Here's a link to additional terminology:
http://www.radford.edu/~rsheehy/cyto...meclature.html

[Birgitta-A]

Hi Darice,
Karen has written a very good info about chromosomes. Here is a link with pictures of our chromosomes:
http://www.thetech.org/genetics/ask.php?id=3

Here is a link where you can read about the prognosis – it is quite old but I think it still is OK:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413090

Kind regards
Birgitta-A

[Darice]

Birgitta-A and Mausmish

Thank you both ever so much . . . this is wonderful information. I'm still making my way through a lot of it, but have learned much so far. I think the pertinent line in my hubby's BMB analysis is:
46,XY,t(6,17)(p22;q25)[4]/45,XY,-7[4]/46,XY[12]

Now, as I understand it, we are analyzing 20 cells here. Four of them have a translocation with parts of chromosomes 6 (area p22) and 17 (area q25) trading places. Another 4 cells have only 45 chromosomes, missing chromosome 7 (and I know this is a bad one to be missing). The other 12 are OK. Is that right? Also, I take it that we have monosomy 7 here, but with only one other abnormality, so it is not considered complex abnormalities. And it is the entire chromosome 7 (one of the two copies, that is) that is missing, not just pieces of it? And is it encouraging that 60% of the cells are "normal" or is that not statistically significant given the smallish sampling?

He has had numerous BMBs in the past, but the diagnosis of the MDS came with a BMB in mid-March 2011 followed by another one in mid-May 2011. I seem to have the printout from the most recent one (May), but the above line comes from a section labeled "Previous Studies" so I am guessing it is from the March BMB. It also has the following two lines:
FISH, Negative for t(14, 18)
FISH Positive for deletion/monosomy7, 30.3% of cells

So why do they specifically test for a translocation of chromosomes 14 and 18 and is it good or bad to be negative for that non-translocation? And why does it show positive for monosomy 7 in 30.3% of the cells when it only notes 4 cells as being positive for monosomy 7 . . . which would be 20% of the cells (30.3% would indicate 6 of the cells positive for monosomy 7)?

Then, we have:
FINAL REPORT
Fluorescence in situ hybridization analysis
Interpretation: POSITIVE for 7q deletion/monosomy 7, 51.5% of cells
D7S486/D7S522 (7q31)-Green, Control/enumeration probe ELN (7q11 23)-Red
1 of 200 cells (0.5%) showed one signal for 7q31 (normal range <5%)
103 of 200 cells showed one signal for 7q31 & one signal for 7q11 (normal range <2%)

It seems that we have jumped to looking at 200 cells rather than 20 and also that now 51.5% of them are positive for the 7q deletion/monosomy 7. The "q" part wasn't in there before . . . is that important? I know I shouldn't freak out about the increase from 20% to 30.3% to 51.5% because we are looking at relatively few cells here and it's not fair to extrapolate 20 or 200 cells to the entire body. But, has something changed with the "q" part? or the talk of "(7q31)-Green" or "ELN (7q11 23)-Red"? And can I assume that because the t(14, 18) isn't listed does that mean the abnormality wasn't found this time around? And would that be good or not statistically significant?

Mausmish:
It looks like Vidaza has worked wonders for you . . . are you still on it or have you been able to stop after a year of "no abnormalities"? Are you considered to be in remission?

Again, thanks for all this great info . . . I'm learning, I'm learning.

[Darice]

I found something in my research where chromosome 7 is related to the particular variety of bladder cancer that Jens has . . . Upper Urinary Tract Urothelial Carcinoma (UTUC), which means that it started in his kidney rather than his bladder . . . and, of course, it is chromosome 7 that is his biggest problem with the MDS. This particular variety is more rare among either the bladder cancer or kidney cancer folks . . . like about 5% of bladder cancers (TCC: transitional cell carcinoma) begin in the renal pelvis (kidney) and also only about 5% of cancers in the kidneys are the TCC-type; most are RCC (renal cell carcinoma). I don't know whether this has any bearing on anything, but it is interesting.

[mausmish]

Hi Darice,

I'm sorry I have no answers for your additional questions but am glad the other info was somewhat useful. I am still learning, too! I just did a quick internet search on t(14,18) - perhaps your husband's doctor was checking for lymphoma?

I was in complete remission after 11 Vidaza cycles and then had a bone marrow transplant Nov. 30, 2010. I had an additional 10 cycles of Vidaza post transplant as part of an informal study - it's believed to help the new immune system to target any potentially remaining cancer cells.

Karen

[Darice]

Hi Karen

Thanks again . . . Yes, he would have been checking for the lymphoma so that makes sense. Jens had NHL since Sep 2001 . . . many recurrences and chemos with stem cell transplant (auto) in May 2008 . . . and all of that was what led to the MDS. Then the drop in blood counts in March of this year . . . doc was suspicious of recurrence of the NHL . . . and found the MDS. I guess the good news is that the NHL is still in remission then.

That is tremendous that you did so well with the Vidaza and then the bone marrow transplant wiped it out with further Vidaza doing a clean up. Wow. I'm guessing you were primary/de novo MDS? I see you have a blog . . . I'll have to get on there and read up on your experiences.

Hadn't occurred to me to do a search for t(14,18) . . . I'll search on some of those other numbers now and see where it goes.

Thanks

Darice

[Greg H]

Hey Darice!

Karen did you a solid with the excellent chromosome primer. Here are a couple of thoughts on your follow-on questions.

20 v. 200. The 20-cell analysis is usually called karyotype. The pathologist culls some cells from the bone marrow aspirate, grows them out in a petri dish or test tube until they are at the point of cell division (which is when you can see the chromosomes) and then picks 20 to isolate and fix up with all the chromosomes in a nice line for analysis. Deciding what's what is done by visual analysis. The pathologist has the whole set of chromosomes laying out in front of her, so she can spot irregularities wherever they occur.

The 200-cell analysis is FISH -- Fluorescence in situ hybridization analysis. Here a special "probe" is created to highlight a specific abnormality in a collection of cells. So, when you do FISH, you test for just one thing. To test for another abnormality, you have to use a different probe. The probe makes the cells that have the abnormality fluoresce in a particular way. Wikipedia has photos. FISH only looks for one irregularity at a time. So it's generally only done to look for the abnormalities associated with a particular disease.

The FISH sample is closer to being big enough to be statistically significant, so the numbers derived from FISH are probably more reliable. But there's a good bit of statistical slop in all of this.

Take care!

Greg

[Darice]

Greg, thanks!

Guess I've been reading and absorbing and it's all finally coming together better.

So, in really really simple terms, they did the March BMB expecting/looking for a recurrence of the NHL. It didn't show up, so while the pathologist had all those lovely (20) cells spread out in all their chromosomal glory she would have looked 'em all over to try to spot any other issues that might have caused the symptoms. This is the karyotype. She probably is beginning to look more specifically for the MDS-related damage because this wouldn't be entirely unexpected given Jens' history. She finds the translocation [t(6,17)(p22;q25)] in 4 cells, which probably isn't all that significant, and the missing chromosome 7 in another 4 cells, which is.

So now we look at the 200 cells, but we're still in the March sample. I'm guessing that the translocation is just kind of pushed aside as contributing to the complex cytology but not critically important of itself. Chromosome 7 now takes center stage. It is a big player . . . everything else kind of doesn't really matter anymore except as it might contribute to complexity. So this is where we get the 30.3% of cells with 7q deletion/monosomy 7 . . . that is something like 61 of the 200 cell sample, not from the original 20-cell karyotype. All this takes more time. Our doc got the negative on the NHL recurrence quite a while back and hasn't worried much further because Jens' blood counts have stayed up pretty well since the March transfusion, there is no evidence of the feared NHL recurrence, and we're concentrating on the other cancer (UTUC).

So the full report finally comes back to our onc/heme who says "Whoa, Nellie! We've got to have another BMB looking more specifically at the MDS issues." He pulls that in mid-May and asks for more specific probes on MDS-related chromosomes . . . and this is where we come up with the 51.5% of the cells (103 of 200) with the 7q deletion/monosomy 7 problem. Now there would be no reason for another BMB until we have reason to believe there might be some change in the cytology, because we now know what's going on.

Think I should be looking for a career in pathology now? Just joking, of course, but I really feel like the past 10+ years must qualify me for something. Anyway, thanks everyone for helping me understand it all better!

[Anne Yeomans]

Hi all
I just been diagnosed with MDS, the only thing I due know is its high risk 1 full blown AML in 4 months. Start Vidaza on the 9th. No hope of survival with out BMT. The longest is 2years the shortest I don;t know. Doc believes its chemo and rad. caused by my first Breast Cancer treatments have had it twice. Don't know counts, not even anything about BMT. Been told my biggest hurdle is the fact that I am on disablitiy Medicare/Medicaid and NO ONE TAKES IT!!!!!!!!!!!!!!!! So I am just to curlup and let the dear Lord take me????????????? Which untill now has never been an option. Don't want to Die Have to much to live for only 52 years old. Don't know where to go from here. PLEASE HELP LOST IN FLORIDA

[Darice]

Hi Anne
Both welcome and sorry you have to be here. The fact that your MDS is a result of the chemo and radiation from your breast cancer makes it secondary or treatment-related MDS which is tougher to treat than the primary or "de novo" MDS which apparently just appears out of the blue. As you can see, this thread is about the chromosome damage that goes along with the MDS and it is stuff that you will be learning more and more about. Have you had a bone marrow biopsy? If so, ask for the results and this will get you started in understanding what's going on. I was just thinking that I was going to copy this entire thread and keep it as a pretty valuable explanation of the chromosome stuff . . . which was all new to me.

My husband is also secondary or treatment-related MDS and has a pretty poor prognosis . . . BUT NONE OF US HAVE EXPIRATION DATES STAMPED ON US ANYWHERE! Do not buy into the gloomy prognosis and, if necessary, find another onc/heme who has a more positive attitude. You need to stay positive in this battle. Jens' prognosis, according to some of the more gloomy statistics I have read, was something like 4-5 months from diagnosis . . . he's about 9 months out right now. And doing well, all things considered.

Get copies of your blood counts . . . the CBCs . . . and start reading. My husband had his stem cell transplant (auto) at 67, and did well . . . it was tough, but we made it. He's 70 now and a good fighter. You've got a lot of fight left in you . . . find a good doc . . . and there are those who will accept medicare/medicaid. Come here with questions . . . there is a wealth of information here.

[mausmish]

Hi Anne - glad to "see" you but sorry for what brings you here. Darice's advice is great. Stay positive.

Darice, you do sound like an expert now! Your summary of the testing sounds spot on. Greg did a nice job of explaining the difference beteen karyotype and FISH. It sounds so simple put in those terms.

Yes, my MDS was de novo, of unknown origin. I've always been amazingly healthy.

[Greg H]

Hey Darice!

You have this chromosome stuff on the run!

On the translocation that was found in the karyotype but not referenced in the FISH: The issue could be that there is no probe commercially available to FISH for that particular abnormality. Specific probes are developed for all the more common and significant abnormalities, but the potential number of abnormalities and probes is, of course, practically infinite, so the probe manufacturers (Abbott seems to be a big one) may not have made one for Jens' translocation.

For example, when I had a BMB with full FISH MDS panel back in September, I asked whether we should do FISH for Chromosome 1, since karyotype had found an abnormality there. NIH's Dr. Matt Olnes said that would be a good idea, but allowed that he wasn't sure a probe was available for my dup(1) (q21:q32). It turned out a probe was available, so that was included in the FISH.

On Monosomy 7: There was an interesting letter and response in a recent issue of the Journal of Clinical Oncology on Monosomy 7 MDS and AML treated with Campath, an immunosuppressant.

Here's the letter from docs at Mayo Clinic in Scottsdale, AZ, and here's a positive response from Olnes and Phillip Scheinberg of NIH. I understand you have bigger fish to fry at the moment, but it might be worth tucking this thought away for later.

Take care!

Greg

[Anne Yeomans]

Originally Posted by Darice

Hi Anne
Both welcome and sorry you have to be here. The fact that your MDS is a result of the chemo and radiation from your breast cancer makes it secondary or treatment-related MDS which is tougher to treat than the primary or "de novo" MDS which apparently just appears out of the blue. As you can see, this thread is about the chromosome damage that goes along with the MDS and it is stuff that you will be learning more and more about. Have you had a bone marrow biopsy? If so, ask for the results and this will get you started in understanding what's going on. I was just thinking that I was going to copy this entire thread and keep it as a pretty valuable explanation of the chromosome stuff . . . which was all new to me.

My husband is also secondary or treatment-related MDS and has a pretty poor prognosis . . . BUT NONE OF US HAVE EXPIRATION DATES STAMPED ON US ANYWHERE! Do not buy into the gloomy prognosis and, if necessary, find another onc/heme who has a more positive attitude. You need to stay positive in this battle. Jens' prognosis, according to some of the more gloomy statistics I have read, was something like 4-5 months from diagnosis . . . he's about 9 months out right now. And doing well, all things considered.

Get copies of your blood counts . . . the CBCs . . . and start reading. My husband had his stem cell transplant (auto) at 67, and did well . . . it was tough, but we made it. He's 70 now and a good fighter. You've got a lot of fight left in you . . . find a good doc . . . and there are those who will accept medicare/medicaid. Come here with questions . . . there is a wealth of information here.

Hi Darice
Yes I've had a bone marrow biopsy about 2wks ago, that's how I got my diag. Still have not got results back as far as geneology. Have more blood work on the 4th start Vidaza Treatment on the 9th. Doc says high stage 1. So far have not been able to find and bmt that takes medicare/medicaid. He's looking in miamia which I believe is the clevland clinic and Tampa which I think is Moffitt not sure. He says baby steps right now. Not sure I can. i work so aggressivly on the breast cancer that the unknown is driving me crazy. Quess I'll have more info after next blood test need to get results so I can try to understand the meaning still very confused. But thanks for info. and may god bless you and your family.

[Glenda H]

My last bone marrow biopsy stated monosomy 7. I was interested to read on another forum about a girl (22months) who was found to have monosomy 7. Is this something that can happen at any time in life or can you be born with it? I was nearly 58 at the time of my BMP.

Regards Glenda H

[Birgitta-A]

Hi Glenda,
As far as I understand most MDS patients don't have inherited MDS. Our chromosome aberrations like monosomy 7 has developed during our lives.
Kind regards
Birgitta-A
del12p and -X