ALLELOTYPE OF HEAD AND NECK PARAGANGLIOMAS - ALLELIC IMBALANCE IS CONFINED TO THE LONG ARM OF CHROMOSOME-II, THE SITE OF THE PREDISPOSING LOCUS PGL

Paragangliomas of the head and neck region are usually slow growing, b enign tumors. A considerable fraction has a positive family history, a nd the predisposing locus, PGL, has recently been assigned to 11q22-q2 3. The inheritance pattern of the disease suggests that PGL undergoes maternal genomic imprinting. We have investigated 26 tumor samples fro m 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 dist al half of the q-arm. However, in many cases the resulting allelic imb alance relative to normal DNA was weak, suggesting that only part of t he tumor showed this abnormality. In all eight cases where we were abl e to determine the parental origin, the allele undergoing loss was mat ernally 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 pol yclonality may explain the partial allele loss events seen in certain cases. Genes Chromosom Cancer 11:71-78 (1994). (C) 1994 Wiley-Liss, In c.