Molecular genetic analysis of tumors in von recklinghausen neurofibromatosis: Loss of heterozygosity for chromosome 17

✍ Scribed by Gary R. Skuse; Barbara A. Kosciolek; Dr. Peter T. Rowley

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 474 KB
• Volume: 1
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870010107

✦ Synopsis

The most common inherited syndrome in man predisposing t o neoplasia is neurofibromatosis-I (von Recklinghausen disease) (NFI). We investigated the hypothesis that affected individuals carry a single inactive allele at the NFI locus in the germline and that a tumor arises from a cell in a susceptible tissue in which the remaining normal allele has been lost or inactivated. DNA from tumor and nontumor tissue from 27 NFI patients was analyzed with three markers closely linked t o the NFI locus and two additional markers from chromosome 17. No loss of heterozygosity was observed in neurofibromas, plexiform or not. For other tumor types analyzed, seven of 14 showed a loss. A loss of heterozygosity was observed in six of I I of the malignant peripheral nerve tumors analyzed. Of the seven malignancies demonstrating a loss, five involved a neurofibrosarcoma. These findings suggest that the pathogenesis of neurofibrosarcoma in NF I involves a deficiency of the NF I gene product. In any given patient, loss of heterozygosity was detected at some marker loci but not others. Thus the mutations demonstrated in these tumors comprise a set of overlapping mutations, which may facilitate more precise localization of the NFI gene.