The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor

We have previously demonstrated allele loss in hamartomas frompatients with tuberous sclerosis for markers spanning the tuberoussclerosis gene on chromosome 16p13.3 (TSC2). Germline deletionsin the TSC2 gene have been shown in 5% of patients with tuberoussclerosis (TSC). These data support our hypothesis that theTSC2 gene acts as a growth suppressor gene, analogous to thetraditional tumour suppressor gene. We now report a TSC hamartomashowing allele loss for markers on chromosome 9q34 in the regionof the TSC1 gene. We studied six hamartomas from four sporadicand two familial cases of TSC, none of which showed allele lossfor markers on chromosome 16p13.3. The hamartomas were paraffinembedded sections of three renal angiomyolipomas, two giantcell astrocytomas, and a cardiac rhabdomyoma. Eight markerswere analysed, comprising from centromeric to telomeric ASS– D9S64 – D9S149 – ABO – D9S150 –DBH – D9S66 – D9S67. One angiomyolipoma showed alleleloss for the markers ABO, DBH and D9S66, but not for D9S149or D9S67. The patient was not informative for D9S150. The familystructure did not permit the phase of the disease and markeralleles to be determined. These finding support the hypothesisthat the TSC1 gene on 9q34, like the TSC2 gene, acts as a growthsuppressor. The data would place the TSC1 gene between D9S149and D9S67. Mapping of allele loss in hamartomas may help inthe refinement of the location of the TSC1 locus.