Reduction of expression of tuberin, the tuberous-sclerosis-complex-gene-2 product in tuberous sclerosis complex associated connective tissue nevi and sporadic squamous and basal cell carcinomas.
BACKGROUND
Patients affected with tuberous sclerosis complex (TSC) are prone to the development of multiple benign tumors of the skin and other organs. Tuberin, the protein product of the tuberous-sclerosis-complex-2 tumor suppressor gene (TSC2) has been shown to inhibit cell proliferation. In TSC associated kidney tumors and sporadic brain tumors the loss/reduction of tuberin has been shown.


METHODS
Specimens of nine squamous cell carcinomas (SCC) and five basal cell carcinomas (BCC) from patients without TSC and six biopsies of connective tissue nevi (CTN) of patients with TSC were obtained. Specimens were analyzed by immunoblotting for the expression of tuberin.


RESULTS
Absent or reduced levels of tuberin were detected in the dermal parts of three of six shagreen patches, two of five BCC, and four of nine SCC.


CONCLUSIONS
In tumors/hamartomas of patients with TSC the complete loss of TSC2 and tuberin is a mechanism which could be shown for CTN, thereby excluding the possibility of haploinsufficiency of TSC2. In a substantial number of cutaneous BCC and SCC the loss or downregulation of tuberin seems to be epigenetic, as alterations of TSC2 are not known in these tumors. The absence or reduction of tuberin might contribute to their proliferation.
Wienecke
Ralf
R
Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, Munich, Germany. Ralf.Wienecke@lrz.uni-muenchen.de
Klemm
Eckart
E
Karparti
Sarolta
S
Swanson
Neil A
NA
Green
Andrew J
AJ
DeClue
Jeffrey E
JE
D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D003238:Connective Tissue / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D015151:Immunoblotting; D018330:Nevus, Intradermal / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D014402:Tuberous Sclerosis / Q000235:genetics / Q000378:metabolism*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D012097:Repressor Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins