Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma.
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. 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. By a molecular genetic approach we have now shown that acoustic neuroma, one of the most common tumours of the human nervous system, 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 autosomal dominant disorder with the hallmark of bilateral acoustic neuromas. 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, we suggest that a common event underlies tumorigenesis in acoustic neuroma and meningioma.
D002872:Chromosome Deletion; D002904:Chromosomes, Human, 21-22 and Y; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007962:Leukocytes / Q000648:ultrastructure; D008297:Male; D008579:Meningioma / Q000235:genetics; D009456:Neurofibromatosis 1 / Q000235:genetics; D009464:Neuroma, Acoustic / Q000235:genetics*
D004273:DNA, Neoplasm; D005819:Genetic Markers