PARAGANGLIOMAS OF THE HEAD AND NECK REGION SHOW COMPLETE LOSS OF HETEROZYGOSITY AT 11Q22-Q23 IN CHIEF CELLS AND THE FLOW-SORTED DNA ANEUPLOID FRACTION

Nonchromaffin paragangliomas of the head and neck region, also known a s glomus tumors, are usually benign neoplasms consisting of clusters o f chief cells surrounded by sustentacular cells arranged in so-called 'Zellballen.' Most of the patients have a familial background. In a pr evious study, examining all chromosome arms, we found loss of heterozy gosity (LOH) predominantly at the chromosome 11q22q23 region, where th e disease causing gene PGL1 has been located by Linkage analysis. Howe ver, all tumors showed only partial loss of allele signal intensities, and it was not clear whether this represented allelic imbalance or ce llular heterogeneity. In the current study, we have performed LOH anal ysis for the 11q22q23 region on DNA-aneuploid tumor cells, enriched by Bow sorting, and on purified chief cell fractions obtained by single- cell microdissection. Complete LOH was found for two markers (D11S560 and CD3D) in the Bow-sorted aneuploid fractions, whereas no LOH was fo und in the diploid fractions of three tumors. The microdissected chief cells from two of these tumors also showed complete LOH for both mark ers, indicating that the chief cells are clonal proliferated tumor cel ls. These results indicate that the PGL1 gene is likely to be a tumor suppressor gene, which is inactivated according to the two-hit model o f Knudson. Furthermore, it shows that chief cells are a major if not t he sole neoplastic component of paragangliomas. Copyright (C) 1998 by W.B. Saunders Company.