Paget's disease and osteosarcoma

[Bex x]

I've been researching how Paget's disease causes osteosarcoma, and I'm having trouble understanding the bit about chromosome 18q21-22 and 23. I think I now understand the bit about the MYC gene and p53... does anyone know what is actually on chromosome 18q21-23? Please? Will give you my eternal love in return...

[pilly84]

Hi Bex

Paget's Disease of the Bone is caused by gene mutations in at least 4 different chromosomes. In particular, PDB2 has been mapped to the long arm of chromosome 18 regions 21-22 (18q21-22). The gene (TNFRSF11A) which is essential for osteoclast formation also maps to the PDB2 region (18q21-22).

Here is where I got that information:

http://www.dent.ucla.edu/ftp/pic/vis...PDB/page1.html

Hope that helps.

[Bex x]

Thanks Pilly, you're a star!

[pilly84]

You're welcome. Glad to help.

[Bex x]

Just out of interest, TNFRSF11A has been shown to be unaffected by changes in 18q21-22, either in Paget's disease or Pagetic osteosarcoma. But they think there's a tumour suppressor gene on there, as LoH in 18q21-22 causes cancer in all sorts of places. So it's probably just that... maybe it's not that Paget's causes osteosarcoma, but people with Paget's may have it due to LoH here, and also get osteosarcoma for the same reason... I don't know, I've been doing this so long I'm guessing now *cries*

[pilly84]

That sounds like a reasonable thing to say. Don't cry! lol

[Bex x]

Why not cry? It may not help, but it's not hindering either - I wasn't getting anywhere anyway.

(I'm not actually crying, or at least, not outwardly... tempting to throw my laptop out of the window, but I won't, Dell are fed up with my little accidents as it is. A big accident like that might make me unpopular!)

[pilly84]

Hmmmmmm, a bit confusing but I have some thoughts on this one.

The 4 known mutations that cause Paget's are:

PDB1 (6p21.3)
PDB2 (18q21-22)
PDB3 (5q35-qter)
PDB4 (5q31)

But the clinical manifestations of each are identical.

Is there the same increase in susceptibility to osteosarcoma with each mutation? If the answer is yes, I would be tempted to say that the main cause of the osteosarcoma (probably a tumour suppressor mutation) would be away from these 4 areas.

Maybe the main culprit for osteosarcoma in these cases is a p53 mutation? This is found at 17p13 and is known to be an early mutation in osteosarcoma.

Hope I'm making sense!

[Bex x]

I've put a bit in about p53, as it's a commonish mutation in Paget's osteosarcoma (or maybe in Paget's in general - can't remember off the top of my head.) I've linked it in to the bit about the MYC gene - MYC is amplified in all studied Pagetic osteosarcomas, some non-Pagetic, and p53 is one of it's receptors. I just thought that as a lot of papers talk about 18q21-22 as well, I'd have a look at that as well.

Sorry, should probably have explained what I already had before I asked...

Also, out of interest, they think there's another gene for Paget's on 18q23, unrelated to 18q21-22.

If anyone else is interested in this stuff, I'll post references - are you studying this stuff too, Pilly, or just helping me out?

[pilly84]

I'm helping you out. Although I'm interested in genetics (I'm intercalating in it next year). Maybe I'm just a bit sad! LOL.