title: [Tests for loss of heterozygosity in tuberous sclerosis].
abstract: The authors assessed loss of heterozygosity in TSC1 and TSC2 genes in three patients undergoing resection of TSC hamartomas: two sub-ependymal giant cell astrocytomas and one kidney angiomyolipoma. Loss with heterozygosity was found only in the patient with kidney angiomyolipoma. A germline mutation, TSC2 E35 645 > A 1549Y > N missense mutation was identified by DHPLC and direct genome sequencing in the blood and loss of the normal allele was demonstrated in the tumor. In one of the patients with brain tumors no germline mutation was identified in the blood, but a heterozygous TSC2 E14 1516C > T 505R > X nonsense mutation was found in the SEGA. Another patient demonstrated germline mutation in TSC2 E38 5116C > T 1706R > C, but tumor DNA indicated that there was retention of heterozygosity for this mutation. The presence of LOH in internal organ tumors is consistent with the Knudson's two-hit model in TS. The frequency of LOH depends on the type of tumor and type of mutation (TSC1 or TSC2).
authors.affiliation: Klinika Neurologii Instytutu Pomnik-Centrum Zdrowia Dziecka w Warszawie. jozwiak@czd.waw.pl
authors.forename: S
authors.initials: S
authors.lastname: Jóźwiak
authors.forename: S
authors.initials: S
authors.lastname: Dabora
authors.forename: J
authors.initials: J
authors.lastname: Kasprzyk-Obara
authors.forename: D
authors.initials: D
authors.lastname: Domańska-Pakieła
authors.forename: W
authors.initials: W
authors.lastname: Grajkowska
mesh_terms: D000293:Adolescent; D002648:Child; D018389:Codon, Nonsense; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000601:surgery; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D018389:Codon, Nonsense; D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins