ALLELIC LOSS IS FREQUENT IN TUBEROUS SCLEROSIS KIDNEY LESIONS BUT RARE IN BRAIN-LESIONS

Tuberous sclerosis (TSC) is an autosomal dominant disorder characteriz ed by seizures, mental retardation, and hamartomatous lesions. Althoug h hamartomas can occur in almost any organ, they are most common in th e brain, kidney, heart, and skin. Allelic loss or loss of heterozygosi ty (LOH) in TSC lesions has previously been reported on chromosomes 16 p13 and 9q34, the locations of the TSC2 and TSC1 genes, respectively, suggesting that the TSC genes act as tumor-suppressor genes. In our st udy, 87 lesions from 47 TSC patients were analyzed for LOH in the TSC1 and TSC2 chromosomal regions. Three findings resulted hem this analys is, First, we confirmed that the TSC1 critical region is distal to D9S 149. Second, we found LOH more frequently on chromosome 16p13 than on 9q34. Of the 28 patients with angiomyolipomas or rhabdomyomas, 16p13 L OH was detected in lesions from 12 (57%) of 21 informative patients, w hile 9q34 LOH was detected in lesions from only 1 patient (4%). This c ould indicate that TSC2 tumors are more likely than TSC1 tumors to req uire surgical resection or that TSC2 is more common than TSC1 in out p atient population. It is also possible that small regions of 9q34 LOH were missed. Lastly, LOH was found in 56% of renal angiomyolipomas and cardiac rhabdomyomas but in only 4% of TSC brain lesions. This sugges ts that brain lesions can result from different pathogenic mechanisms than kidney and heart lesions.