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Is a transcript type different from a mutation?

My transcript type is e13a2. Since this number does not occur in the mutation list provided elsewhere in this forum, I rather presume that  "transcript type" is different from a mutation. Can anyone, please, describe in simple terms the definition of "transcript type"?

Good question. And what is the difference between a ”transcript type” and a mutation? 

I presume that medical students must learn some basics which are not addressed in the various scientific papers. I surmise that the "transcript type" is associated with breakpoints in the chromosome (there is reference to "exons" as the defining points in the various narratives). One study indicates that 42% of us are e13a2, 41% e14a2 and 18% a bit of each.

The mutations appear to occur in the kinase domain of ABL1.

I am not so sure whether the kinanse domain mutations result from further changes within the chromosome or whether there is a coding regularity.

I am in need of Haematology for Dummies.

Hello, 

transcript type in this case is result of new fused chromosome. Well known Ph chromosome. The breakage of 9 and 22 can be in a little different places... few DNA bases back or forward but still in place of ABL and BCR gene. This little differences codes different transcript types, but both lead to the same product - protein p210, if it breaks more next it could lead to p190 which result in acute lymphoblastic leukemia . In medical terms, everything is mutation. The initial breakage is mutation. 

Each CML patient has any of mentioned transcript types (e13a2, e14a2 ...) at the beginning of the disease and the presence of it does not mean any evolution (any further new mutations), it is just more precise categorization of the disease behind simoly Ph+. 

Hope this was helpful. 

Eva

Thank you, Eva, this is exactly what I wanted to try to understand. This plugs one gap in my knowledge.

All transcript types are the result of DNA mutations. The so-called Philadelphia chromosome is the result of a translocation mutation where a piece of DNA from one chromosome is swapped onto another. The breakpoint is the region on chromosome 22 (abl gene) where the split occurs and the nomenclature "p190" or "p210" is the resulting molecular weight of the new bcr-abl protein a direct result of this new gene. There are more than 20 breakpoints associated with CML with the vast majority being the ones you list.. There is debate on how the different forms of bcr-abl caused by the different breakpoints results in different CML activity (neutrophilic, etc.), but p190 is considered the most potent form.

Additional information which may be helpful:

https://www.dnalc.org/view/1241-Breakpoints.html

Description:

Professor David Porteous explains that breakpoints in the genome are locations on a chromosome where DNA might get deleted, inverted, or swapped around.

Transcript:

Well, we use the word breakpoint to indicate that the human genome, which we now understand in terms of a set of chromosomes - 22 pairs plus the sex chromosomes - the x and y. The standard notion is that we have a complete set of those chromosomes and that they have a very clear structure but occasionally we see damage to those chromosomes. Sometimes we get so-called breakpoints in those chromosomes and that leads to damage at a very particular point within the genome on one or other chromosome. And it can take several different forms. It might be that you lose a whole segment of a chromosome, what we call an interstitial deletion. It might be that a piece of the DNA chromosome segment gets flipped around, a so-called inversion. Then there's a very interesting form of rearrangement, which we call a translocation, translocation moved position. So we see a piece of one chromosome move over to another chromosome and swap. So the genome is intact but there's a very precise breakpoint where there's a discontinuity in the genome from the normal.

But what about this nomenclature:

https://images.app.goo.gl/FzYSnFeaqAbh54fS8

or

https://www.google.com/search?q=cml+mutation+tki&rlz=1CDGOYI_enSE592SE59...

when you talk about ”T315I” etc. What is that compared with ”P210” etc.?

Thank you, Scuba, your posting is very helpful and has helped me do more googling.

I found the following:

Schematic diagram of the position of specific primers on the exons of BCR and ABL used in the multiplex RT-PCR assay for the detection of major fusion transcript in patients with CML.

https://www.researchgate.net/figure/Schematic-diagram-of-the-position-of...

Of course, we are most interested in 13 and 14.

Deleted by Nimbus2 because my observation is incorrect.