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 characterist ic feature is the development of multiple hamartomas in a variety of o rgans and tissues. Two major loci have been identified so far: TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13.3. Loss of heterozygosit y at 16p13.3-associated markers has been recently observed in hamartom atous lesions of some tuberous sclerosis patients. Here we report the first evidence of loss of heterozygosity at the TSC1 critical region i n a giant cell astrocytoma of a familial tuberous sclerosis case. Segr egation analysis showed that the 9q34 haplotype lost carried the putat ive normal TSC1 gene. These data support the hypothesis of both a germ line and somatic loss-of-function mutation for the development of tube rous 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.