9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene.
Tuberous sclerosis is an autosomal dominant disease whose characteristic feature is the development of multiple hamartomas in a variety of organs and tissues. Two major loci have been identified so far: TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13.3. Loss of heterozygosity at 16p13.3-associated markers has been recently observed in hamartomatous lesions of some tuberous sclerosis patients. Here we report the first evidence of loss of heterozygosity at the TSC1 critical region in a giant cell astrocytoma of a familial tuberous sclerosis case. Segregation analysis showed that the 9q34 haplotype lost carried the putative normal TSC1 gene. These data support the hypothesis of both a germline and somatic loss-of-function mutation for the development of tuberous sclerosis hamartomas and suggest a tumor-suppressor-like activity also for the TSC1 gene product. Finally, the possible significance of a second small region of loss of heterozygosity at 9p21, found in the same astrocytoma, is discussed.
CNR Centro Immunogenetica ed Oncologia Sperimentale, Università di Torino, italy.
C
C
Carbonara
L
L
Longa
E
E
Grosso
C
C
Borrone
M G
MG
Garrè
M
M
Brisigotti
N
N
Migone
D001254:Astrocytoma / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D002899:Chromosomes, Human, Pair 9; D005260:Female; D016153:Genes, Suppressor; D006222:Hamartoma / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D014402:Tuberous Sclerosis / Q000150:complications / Q000235:genetics*