Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma

• Published in: Nature (London) 1986-08, Vol.322 (6080), p.644-647
• Main Authors: Seizinger, Bernd R, Martuza, Robert L, Gusella, James F
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, 21-22 and Y; DNA, Neoplasm - analysis; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Female; Genetic Markers; Humanities and Social Sciences; Humans; letter; Leukocytes - ultrastructure; Male; Medical sciences; Meningioma - genetics; multidisciplinary; Neurofibromatosis 1 - genetics; Neuroma, Acoustic - genetics; Otorhinolaryngology. Stomatology; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/322644a0

The application of recombinant DNA techniques has identified two fundamental mechanisms of tumorigenesis in man. The first involves a qualitative or quantitative change in an oncogene (see ref. 1 for review). In the second, discovered in embryonal tumours, a primary mutation occurs which is recessive at the cellular level to the normal allele. The growth of a tumour ensues only after a secondary change, such as chromosome loss or mitotic recombination, eliminates the normal allele, thereby unmasking the altered allele 2–7 . Because its effect is recessive, the primary mutation may also occur and be transmitted in the germ line, resulting in a familial pattern for the disease. In familial cases, independent bilateral tumours are common, since the tumours result from a single event—loss of the normal genes—which can occur in any cell. This contrasts with non-familial (sporadic) cases where solitary tumours result from the infrequent occurrence of two rare events within the same cell 2–7 . By a molecular genetic approach we have now shown that acoustic neuroma, one of the most common tumours of the human nervous system 8 , is specifically associated with loss of genes on human chromosome 22 and may result from the mechanism of tumorigenesis discovered in embryonal tumours. This finding might provide a clue to the chromosomal location of the defective gene in bilateral acoustic neurofibromatosis, an auto-somal dominant disorder with the hallmark of bilateral acoustic neuromas 9–12 . In view of the frequent occurrence of meningiomas in patients with bilateral acoustic neurofibromatosis and the association of meningioma with loss of chromosome 22 previously reported in cytogenetic studies 13–15 , we suggest that a common event underlies tumorigenesis in acoustic neuroma and meningioma.