Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas

Caterina Carbonara, Lucia Longa, Enrico Grosso, Gianna Mazzucco, Carla Borrone, Maria Luisa Garrè, Massimo Brisigotti, Giorgio Filippi, Aldo Scabar, Aldo Giannotti, Piero Falzoni, Guido Monga, Gianni Garini, Marzio Gabrielli, Peter Riegler, Cesare Danesino, Martino Ruggieri, Gaetano Magro, Nicola Migone

Research output: Contribution to journalArticlepeer-review


To investigate the molecular mechanisms of tuberous sclerosis (TSC) histopathologic lesions, we have tested for loss of heterozygosity the two TSC loci (TSC1 and TSC2) and seven tumor suppressor gene-containing regions (TP53, NF1, NF2, BRCA1, APC, VHL, and MLM) in 20 hamartomas from 18 TSC patients. Overall, eight angiomyolipomas, eight giant cell astrocytomas, one cortical tuber, and three rhabdomyomas were analyzed. Loss of heterozygosity at either TSC locus was found in a large fraction of the informative patients, both sporadic (7/14) and familial (1/4). Interestingly, a statistically significant preponderance of loss of heterozygosity at TSC2 was observed in the sporadic group (P <0.01). Among the possible explanations considered, the bias in the selection for TSC patients with the most severe organ impairment seems particularly appealing. According to this view, a TSC2 defect might confer a greater risk for early kidney failure or, possibly, a more rapid growth of a giant cell astrocytoma. None of the seven antioncogenes tested showed loss of heterozygosity, indicating that the loss of either TSC gene product may be sufficient to promote hamartomatous cell growth. Finally, the observation of loss of heterozygosity at different markers in an astrocytoma and in an angiomyolipoma from the same patient might suggest the multifocal origin of the second-hit mutation.

Original languageEnglish
Pages (from-to)18-25
Number of pages8
JournalGenes Chromosomes and Cancer
Issue number1
Publication statusPublished - Jan 1996

ASJC Scopus subject areas

  • Cancer Research
  • Genetics


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