Media type: E-Article Title: Multiple meningiomas: Investigating the molecular basis of sporadic and familial forms Contributor: Heinrich, Bianca; Hartmann, Christian; Stemmer‐Rachamimov, Anat O.; Louis, David N.; MacCollin, Mia Published: Wiley, 2003 Published in: International Journal of Cancer, 103 (2003) 4, Seite 483-488 Language: English DOI: 10.1002/ijc.10840 ISSN: 0020-7136; 1097-0215 Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>Meningiomas are common tumors of the coverings of the central nervous system (CNS), comprising 20% of intracranial neoplasms. The only genes known to be associated with sporadic meningiomas are <jats:italic>NF2</jats:italic> on chromosome 22 and the related cytoskeleton element <jats:italic>DAL‐1</jats:italic> on chromosome 18. Between 1 and 8% of patients with meningiomas develop multiple meningiomas, a trait transmitted occasionally in an autosomal dominant fashion. We investigated the <jats:italic>DAL‐1</jats:italic> and <jats:italic>NF2</jats:italic> loci in 7 unrelated multiple meningioma patients without clinical evidence of NF2 by mutational and pathological analysis. Five novel intragenic microsatellite polymorphisms were developed for specific detection of loss of heterozygosity (LOH) at the <jats:italic>DAL‐1</jats:italic> locus. Three of 7 patients had affected relatives and all affected individuals were female. No tumors from familial patients were of a fibroblastic subtype. Truncating <jats:italic>NF2</jats:italic> mutations were detected in 3 tumor specimens, but were not present in the corresponding blood samples. Two tumors showed LOH at the <jats:italic>NF2</jats:italic> locus. All tumors showing mutations at the <jats:italic>NF2</jats:italic> locus originated from patients without affected relatives and were of the fibroblastic subtype. Five non‐truncating alterations in the <jats:italic>DAL‐1</jats:italic> gene were found, however, LOH of chromosome 18 markers was not seen in any tumor. In contrast to the <jats:italic>NF2</jats:italic> results, all <jats:italic>DAL‐1</jats:italic> alterations were found in paired blood specimens. Our findings provide further evidence that the molecular basis of sporadic and familial multiple meningiomas is fundamentally different and extend this dichotomy to pathologic subtypes. <jats:italic>DAL‐1</jats:italic> does not function as a true tumor suppressor in these patients. © 2002 Wiley‐Liss, Inc.</jats:p> Access State: Open Access