Nf1

[tanman09]

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Question about Neurofibromatosis type I -
First aid has it listed under tumor suppressor genes that need both alleles to be lost to express disease but NF1 is an autosomal dominant disease. In my mind, these two points seem contradictory - what am I missing?

 

[maninthemirror]

That's a pretty good question. The bottom line is that not everything very clear cut.

Here's the thing. NF1 codes for a tumor suppressor gene that is a Ras GTP-ase. So, it makes sure that the tumor oncogene Ras is kept in an inactive state by dephosphorylating it. Now if you have a mutation in Ras-GTPase on one chromosome only, the Ras oncogene is more active (the other Ras-GTPase probably can't keep up as well).

Bottom Line: You're not just inactivating a tumor suppressor gene. You're also upregulating a tumor oncogene (Ras) a bit in the process. The fact that the other NF1 gene can't keep Ras under control seems to suggest that this isn't one of those classic tumor suppressor genes that require 2 hits.

Disclaimer: The above is mostly just speculation on my part.

 

[jfgavina]

maninthemirror I hope that goes beyhond the spectrum of step 1 contents lol

 

[Suncrusher]

From what I understand, any tumor supressor mutation that is dominant is most likely to be a case of hemi-insufficiency, like the second poster said. any decrease in the levels of the tumor supressor (like 1 allele getting mutated) causes enough decrease in activity that the oncogene it is supposed to be keeping in check starts running wild

of course, there are a few cases I know of where tumor supressor mutations are dominant by another mechanism, such as lynch's syndrome. The mutation is in a tumor supressor gene that repairs DNA bp mismatches, and if you are born with 1 mutated allele, the odds are simply overwhelming that an exogenous or endogenous mutation will lead to a hit on the second allele in at least one of the 10 trillion cells of your body, at which point the mutations in that cell will run wild. So the disease appears dominant--due to the overwhelming odds of a second hit--even though it is really recessive (because until that second hit happens, the one normal allele is sufficient to keep the mutations in check)

please correct me if I'm wrong! : )

 

[ctizzle13498]

hahaha i hope so too...all im learning is

NF1- Von Recklinghausen's Disease differerent from Von Rechlinghausen's Syndrome (osteitis fibrosa cystica)

NF2- bilateral acoustic shwannoma

 

[maninthemirror]

maninthemirror I hope that goes beyhond the spectrum of step 1 contents lol

Well, it was mostly just speculation.

It's probably worth knowing that NF1 codes for a RAS GTPase that dephosphorylates Ras. And that it can be inherited in AD form.

They probably won't ask you WHY its AD. It is what it is.