Molecular Genetic Approach to Human Meningioma: Loss of Genes on Chromosome 22

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 15; pp. 5419 - 5423
• Main Authors: Seizinger, Bernd R., De La Monte, Suzanne, Atkins, Leonard, Gusella, James F., Martuza, Robert L.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-08-1987; National Acad Sciences
• Subjects: Acoustic neuroma; Biological and medical sciences; Brain Neoplasms - genetics; Chromosomes; Chromosomes, Human, Pair 22; Cytogenetics; DNA; DNA probes; DNA Restriction Enzymes - metabolism; Fundamental and applied biological sciences. Psychology; Genes; Genetic Carrier Screening; Genetic loci; Genetic Markers; Genetics of eukaryotes. Biological and molecular evolution; Human; Humans; Leukocytes; Meningioma; Meningioma - genetics; Molecular genetics; Neurofibromatosis 1 - genetics; Nucleic Acid Hybridization; Oncogenes; Tumors; Human; Cytogenetics; Deletion; Gene; Meningioma; G22-Chromosome
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.15.5419

A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, we propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.