Whole genome sequencing

[Guest guest]

Can this technology help patients with CLL?

http://jama.ama-assn.org/content/305/15/1596

carla

[Guest guest]

It is being done every day... the process is called aCGH.

(array - Comparative Genomic Hybridization)

Here is a commercial example: Heme Profile... many companies

are developing these...

http://www.combimatrix.com/oncology/hemeprofile.html

In a couple of years there will be a hand held microarray

that will give your TP53 gene mutation status...AmpliChip

p53 is currently in the testing stages.

http://onlinelibrary.wiley.com/doi/10.1002/gcc.20852/full

HTH

~chris

[Guest guest]

This testing will give information pertaining to CLL as well

as indicators of genome instability, and other possible,

related cancers that may have been missed on traditional

FISH testing, either because the issue was not a suspect, or

due to various technical problems with FISH testing. FISH

can and is done for many conditions as is Acgh. The

difference is Acgh tests the entire genome. FISH one must

choose.

If one goes to the link put on the list, and reads Dr.

Gunn's research, you will see that some chromosomal

abnormalities are missed during FISH testing. This is due

to many factors such as defective 'probes', operator error,

incorrect interpretation etc. One that seems to be most

commonly missed is 11q and it's varieties. Wikipedia covers

the process of FISH testing well, explaining it in language

that is easily understood.

http://en.wikipedia.org/wiki/Fluorescence_in_situ_hybridization

As a friend of mine who is a pathologist said, " the

trouble with FISH testing is one first must know what one is

fishing for " .... Traditional array used for CLL is limited

to the usual suspects. The wide array has the potential to

see things that one might not expect to find in vanilla

flavor CLL.

I was one such case. At diagnosis I was told I had no

deletions. Within just over a year, even though my wbc was

only moderately climbing, my nodes were growing and showing

up in all regions. From what I had learned this did not fit

with 'no deletions' but rather seemed like an 11q might be

lurking. There were other indications as well, such as a

rising B2m, and a pos zap 70 at 90%, which also was not

there at diagnosis. I read about this test and managed to

have it done. The 11q was there, along with a trisomy 8 and

a missing ATM on the 11q. My 11q was also not typical.

the report stated, unstable, moderately aggressive CLL.

This was a far cry from what I had originally been told just

two years before. It is possible that the original testing

was correct, since I had FISH done twice, both at top CLL

centers. Morphing can take place at any time in CLL.

However, the way my CLL was behaving, or mis behaving, it's

also possible that Dr. Gunn's observations fit this

situation, a missed 11q. Trisomy 8 would not have been

found on the first two FISH tests since this is an indicator

more associated with MDS, and myloid cancers, not CLL. At

least it has not been. There have been posts of people

having this discovered 'after' treatment with some of the

more ablative drugs. Hence it might be a good idea to find

out if it's there prior to embarking on those protocols.

On the Myloid note, the same testing can be done on Marrow,

and for myloid cancers that is what they would do. The

blood indicators are just indicators. IF found in the blood

then the idea is to confirm that the actual problem has

manifested itself in the Marrow.

The benefits of this test to a CLL patient are there. As

the research world tries to discover more targeted, kinder,

treatments this type of testing will become the standard,

but there's no reason not to begin using it now, and

compiling data on some of the deletions and additions that

may prove more common in CLL than had been assumed and that

may have been missed with traditional FISH testing. This

type of testing is less dependent on operator error, faulty

probes, and since it covers the entire genome it is more

complete. It is also much faster and less costly in many

instances, even now. In case anyone is wondering, my

hemescan results were confirmed by traditional fish as well;

removing any doubt as to the accuracy of the 'newer'

testing. MD has worked with Combimatrix on some

of their development. There are probably some centers

where this type of testing is available now, I just don't

know off hand which ones. If anyone does and wishes to

post those it would be helpful to some of us. As Chris

pointed out, wide array, Acgh, will be more widely available

at some point.

all the best, Beth Fillman