Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions.

摘要: Tuberous sclerosis complex (TSC), an autosomal dominant disease caused by mutations in either TSC1 or TSC2, is characterized the development of hamartomas a variety organs. Concordant with tumor-suppressor model, loss heterozygosity (LOH) known to occur these at loci both and TSC2. LOH has been documented renal angiomyolipomas (AMLs), but wild-type allele cortical tubers appears be very uncommon. Analysis second, somatic events tumors for which status TSC2 essential exploration pathogenesis TSC-lesion development. We analyzed 24 from 10 patients second-hit mutations, several methods, including LOH, scanning all exons promoter methylation clonality analysis. Our results document six seven AMLs, without evidence inactivation second many other lesions, that appear clonally derived. Laser-capture microdissection further demonstrated three cellular components AML. This study thus provides that, resulting alleles may not necessary some tumor types—and mechanisms contribute tumorigenesis this setting.