Last year, when I met my hematologist for the first time, he told me my CLL was indolent. W/W is where things stand. Looking at the information below, one would think I'm 'normal'. I know I'm not. I have CLL. Anyway, what the heck does the info below really mean? I am 65 yo male and IgHV unmutated. Thanks for any/all feedback.
CLL, FISH
: Result Summary - Normal
Interpretation
: The result is within normal limits for the CLL FISH panel and the CCND1 and IGH gene regions.
Cll is caused by a chromosome abnormality. FISH looks for the most common abnormalities. Your FISH test looked at the regions of chromosomes 6, 11, 12,13 and 17 where some missing or added genetic material is usually found with cll. Your FISH test was normal, meaning you do not have one of the typical chromosomal abnormalities.
A normal FISH does not mean you do not have a defect somewhere in some chromosome. You have cll so you almost certainly have a chromosomal defect. So why doesn't FISH look at every region of every chromosome? I think that is because that would be an enormously expensive and time consuming thing to do. Gardening Girl might could better explain what would be involved in looking at that. We have 25000 genes in our chromosomes, FISH just looks at a handful of them.
People with cll and a normal FISH are thought to have an intermediate prognosis, not as good as 13q deleted alone, but better than 17p deleted.
You are very welcome. I might add that how our cll actually does is way more important than what our markers predict it will do. Its hard to put "normal" FISH results into any risk bucket because the area of the defect is unknown.
Your doctor has described your cll as indolent, meaning to me that he is observing that your cll progresses slowly. To me, the fact your cll actually acts in an indolent way is the most important predictor.
Great link Jeff, to Chaya's discussion of the FISH test. As both you and Chaya point out the typical CLL FISH panel only looks at major chromosomal deletions, additions or rearrangements. To look for teeny, tiny defects in genes & chromosomes, for example, single nucleotide base changes that can profoundly alter gene or protein function, DNA has to be sequenced.
Most of the DNA sequencing for CLL outside clinical trials targets a few genes that have been shown to have prognostic significance, for example sequencing ATM, BIRC3, NOTCH1, SF3B1, and TP53 genes.
The link below is an interesting discussion of CLL Diagnostics: Next-Generation Sequencing (NGS) of TP53
For academic studies of CLL, companies such as Genoptix offer a CLL Comprehensive Panel that sequences parts of about 50 genes by NGS technology. There have also been whole genome sequencing (WGS) and whole exon sequencing (WES) studies done on CLL cells, but this is quite rare and generates massive amounts of data.
Good stuff GG. The term "sequencing" is confusing to me and others, but I get the gist.
In the context of this discussion, a FISH test picks out five or so genes to look at and they know where the genes are located at on our chromosomes to find them.
GG, it appears that in the "man with a plan's" case, all these five genes were normal. So if we wanted to go fishing to find what gene he had that was damaged to create his cll, would one have to look at thousands upon thousands of genes to find it?
How long would it take to "sequence" thousands of genes? What would the cost be? Can you simply the term "sequence a gene" and what it means in layman's terms?
I think some people with a so called "normal" FISH test can be confused as to why their abnormal chromosome/gene cannot be discovered.
Jeff, the short answer to your question about DNA sequencing is that sequencing DNA simply means determining the order of As, Ts, Cs and Gs in a stretch of DNA.
Clinical whole-exome sequencing that sequences only the genes that are being expressed at any given time costs maybe $500, and whole-genome sequencing could cost maybe $1000. The actually sequencing is fast..a day or two, but if cells have to be grown in culture first, it can be days before the sequencing is done.
Then of course there is always the problem of analyzing the data! As far as I know, no one knows what specific mutations cause CLL. As you know there are the mutations to which I referred above (ATM, BIRC3, NOTCH1, SF3B1, and TP53 ) that could provide prognostic information and those, especially the TP53 mutation should be sequenced before any treatment decision is made.
I am going to use the p53 gene as an example of what a DNA sequence looks like with the As, Ts, Cs & Gs representing the four nucleotides that make up DNA, and then I’ll highlight the most frequent p53 mutation in CLL.
First I need to define a codon. A codon is a three nucleotide sequence that specifies a particular amino acid. In the sequence below, codon 1, the sequence of which is ATG (underlined below), codes for the amino acid methionine (M) and Codon 2, GAG, codes for glutamic acid (E), ETC!
In p53 there are six ‘hotspot’ codons (175, 245, 248, 249, 273, and 282) associated with CLL.
Because of a single base change from guanine (G) to adenine (A) in the p53 gene at codon 175, the amino acid histidine (H) replaces the amino acid arginine (R) in the resulting TP53 protein. That causes the shape of the protein to change, interfering with its ability to bind to DNA and guard the genome.
Nucleotide Sequence of the human p53 gene (1182 nucleotides long) with codon 175 marked as
To gain a basic understanding of DNA, RNA and proteins, and the processes by which information in genes is translated into proteins, I highly recommend this site:
Dr. Furman did order a Genoptix panel. I looked at the results 3-4 different times. Honestly, it's all Greek to me. Waaaay too much data for this CLL neophyte. He and I have never discussed the results. (Honestly, I'm lucky if I talk to him for 20-30 minutes every 6 months.) Perhaps my genetic signature has scientific value. During my first visit back in 2019, I agreed to participate in any/all Weill Cornell/NY Presbyterian CLL studies.
Anyway, thanks for your in-depth feedback. Having you and Cajun Jeff as my CLL 'consultants' is a real bonus.
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Interpreting blood results
Results back from the FISH
TREATMENT OPTION FOR TRISOMY 12
Fishing
All normal fish report. No deetions 
