Tuberous sclerosis-TSC2-Help!?!

Thomas Haag thaag at pathology.medsch.ucla.edu
Wed Oct 18 13:48:36 EST 1995


I'm a graduate student starting out doing some research on Tuberous
sclerosis and the function of the TSC2 gene.  I have read that the
gene works as a classic tumor-suppressor gene, requiring a two-hit
somatic mutation, and subsequent loss of heterozygosity.  Apparently,
this results in a clonal expansion of TSC2 negative cells forming the
tubers, hamartomas and body-wide benign tumors.  Now my question is
that why has it been found the TSC2 (mRNA) is overexpressed in the
pyrimidal cells of the cerebral cortex in the hamartomas?  Does anyone
think that it leads to a truncated or junk protein?  If so why only in
pyramidal cells if the two-hit hypothesis results in clonal expansion
(meaning all cells in the hamartoma have the same genotype)?  I have
done TSC2 in situ hybridizations on young (13day) mice and (17day)
embryos.  In both cases there is large amounts of TSC2 mRNA
expression.  This dosen't sound like a tumor suppressor gene, rather
it sounds like the Rap1GAP activation protein, that Wieneke et. al.
say it has homolgy to.  Can anyone help a confused 1st year grad
student?
Thomas Haag
thaag at pathology.medsch.ucla.edu
   




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