chromosomes

The Professors' Posts

Chromosomes

SUSAN LECLAIR

Ah, Tom, have you opened up a can of worms! The nomenclature system for genes sounds simple but when you add in specific mutations it is really a horrid mess.

So - just the rules for chromosomes - (A semi-colon separates two chromosomes)

Rule #1 All chromosomes are numbered based on their size and location of where the two strands cross. So chromosome number 1 is the largest and the two parts of the "X" cross in the middle - just like an "X"(this is called the centromere). Chromosome 2 is also large but the strands cross in the upper half of the x - which I can't draw here. Chromosome 3 is large and the centromere is at the edge.

Groups of chromosomes that look something alike were grouped A through G so sometimes you would say/hear about a G group chromosome or a G;D translocation.

Rule #2 The bottom (and usually larger portion of the chromosome) is referred to the "q" while the upper (and usually smaller portion of the chromosome) is referred to as the "p". One way I tell my students to remember this is that the p stands for petit.

So - if you are missing the short arm of chromosome number 1, it would be "said" as del (1p). If you have a piece of chromosome 14 that was translocated to chromosome 18, it would be said as t(14;18).

But since most folks are lazy speakers, the short hand for a mutation that "EVERYBODY" knows you really mean would be 14;18.

Now - for specific mutations

A stain that causes differences in staining (light and dark) divides chromosomes into bands. Bands are counted from the centromere so you will have band #1 above the centromere and band #1 below the centromere. In order to make that clear - for chromosome 1 - band #1 above the centromere is called 1p1 and band #1 below the centromere is called 1q1.

Now - we can subdivide the bands so on chromosome number 1, the band above the centromere with a total of 15 bands each with some number of subbands. So you could have a problem with chromosome #1, the first subband of band number 1 on the short arm and its name would be 1(p1.1).

Now that you have a headache - the biggest issue for CLL folks at the moment is the translocations such as 14;18 which means that a piece of chromosome 14 has been moved to chromosome 18. And forget the rest! ;-)

TERRY HAMBLIN

Del is short for deletions and is an over simplification. It means that there has been some chromosomal loss. Sometimes a great chunk of the chromosome is missing sometimes only a couple of genes. Sometimes the missing piece of chromosome has been relocated to another chromosome, but his usually means that something has been lost in the process.

Chromosomes come in pairs so if you lose a gene from on e chromosome you have a spare on its pair. Unfortunately the spare is often damaged even thoughit is physically still there. Some genes don't work properly if even one copy is lost; a good example is p53 at chromosome 17p13.

In CLL the commonest deletions are at 13q14 (this actually improves prognosis), 11q23 and 17p13. The gene at 13q14 is not known. there are 5 genes at this location and none of them seems to fit the bill, but the best minds on the planet are working on it. At 11q23 the ATM gene is implicated, though some people think that theer are other genes here that may be more important in some cases of CLL. At 17p13 p53 is involved.

ATM and p53 act along the same molecular pathway and when they are missing the prognosis is worse. Most people find that del17p13 is worse than del11q23.

TERRY HAMBLIN

A cytogenetic analysis enables chromosomes to be analyzed individually.
Normally the chromosomes in the nucleus of a cell are all jumbled up together and
cannot be separately distinguished. It is only when a cell divides that the
chromosomes line up and separate. This process is known as mitosis and it has
to occur in order to examine the chromosomes. CLL cells in the blood do not
divide, and have to be induced to do so by substances called mitogens. When
white cells are examined for chromosomal abnormalities like the three #21s in
Down's syndrome, a mitogen called PHA is used. Unfortunately CLL do not
respond to PHA. In a lot of the early studies some 30 years ago, PHA was used, but
the only cells that went into mitosis were the normal T cells. The hunt was
then on for a mitogen that would make CLL cells divide. Early favorites were
pokeweed mitogen and EB virus, until they hit on phorbol ester (also known as
TPA). Even now there are very few labs world-wide who are very good at the
assay (I think only our lab does it routinely in the UK). One of the things
that EB virus was prone to do was to cause tetraploidy as an artefact. In fact
true tetraploidy is incredibly rare in CLL.

Because chromosome analysis is so difficult in CLL, most labs have gone over
to FISH, which stands for Fluorescent In Situ Hybridisation. With FISH the
cells don't need to divide. But you only find abnormalities that you look for.
Most labs only probe the cells for chromosomes 11,12, 13 and 17 (some add 6)
and therefore abnormalities other than these are not found.

The white count is irrelevant in CLL. The NCI guidelines clearly state that
the height of the white count should not be used as an indication for
treatment.

TERRY HAMBLIN

Dear Diana,

A cytogenetic analysis enables chromosomes to be analyzed individually. Normally the chromosomes in the nucleus of a cell are all jumbled up together and cannot be separately distinguished. It is only when a cell divides that the chromosomes line up and separate. This process is known as mitosis and it has to occur in order to examine the chromosomes. CLL cells in the blood do not divide, and have to be induced to do so by substances called mitogens. When white cells are examined for chromosomal abnormalities like the three #21s in Down's syndrome, a mitogen called PHA is used. Unfortunately CLL do not respond to PHA. In a lot of the early studies some 30 years ago, PHA was used, but the only cells that went into mitosis were the normal T cells. The hunt was then on for a mitogen that would make CLL cells divide. Early favorites were pokeweed mitogen and EB virus, until they hit on phorbol ester (also known as TPA). Even now there are very few labs world-wide who are very good at the assay (I think only our lab does it routinely in the UK). One of the things that EB virus was prone to do was to cause tetraploidy as an artefact. In fact true tetraploidy is incredibly rare in CLL.

Because chromosome analysis is so difficult in CLL, most labs have gone over to FISH, which stands for Fluorescent In Situ Hybridisation. With FISH the cells don't need to divide. BUt you only find abnormalities that you look for. Most labs only probe the cells for chromosomes 11,12, 13 and 17 (some add 6) and therefore abnormalities other than these are not found.

The white count is irrelevant in CLL. The NCI guidelines clearly state that the height of the white count should not be used as an indication for treatment.

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