Allelotype of head and neck paragangliomas: allelic imbalance is confined to the long arm of chromosome 11, the site of the predisposing locus PGL.

Paragangliomas of the head and neck region are usually slow growing, benign tumors. A considerable fraction has a positive family history, and the predisposing locus, PGL, has recently been assigned to 11q22-q23. The inheritance pattern of the disease suggests that PGL undergoes maternal genomic imprinting. We have investigated 26 tumor samples from 22 patients with head and neck paragangliomas for the occurrence of loss of heterozygosity (LOH) on all non-acrocentric autosome arms. LOH was found only on chromosome 11, with a marked clustering on the distal half of the q-arm. However, in many cases the resulting allelic imbalance relative to normal DNA was weak, suggesting that only part of the tumor showed this abnormality. In all eight cases where we were able to determine the parental origin, the allele undergoing loss was maternally derived. Clonality analysis with a polymorphic marker for the X-chromosome indicated that two of three informative female cases were polyclonal, although a number of tumors carry aneuploid stemlines in DNA flow cytometry. We conclude that either tumor heterogeneity or polyclonality may explain the partial allele loss events seen in certain cases.