Biallelic TSC gene inactivation in tuberous sclerosis complex.

ABSTRACT:

Background

A pivotal developmental question is whether tubers in tuberous sclerosis complex (TSC) form by germline and somatic TSC1 or TSC2 gene mutations. Loss of TSC1 or TSC2 in vitro and in vivo leads to mTORC1 cascade activation and ribosomal protein S6 phosphorylation (P-S6). Giant cells (GCs) in tubers exhibit S6 phosphorylation, suggesting cell-specific loss of TSC gene function.

Methods

TSC1 and TSC2 gene mutations were investigated in DNA extracted from tuber sections (n = 6) and microdissected P-S6-labeled GCs by sequencing and loss of heterozygosity (LOH) analysis to define germline and somatic mutations.

Results

A germline TSC1 mutation was defined in 1 case and TSC2 mutations were defined in 5 cases. LOH was not detected in whole tuber sections or microdi

SUBMITTER: Crino PB 

PROVIDER: S-EPMC2882213 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature