Differential loss of chromosome 11q in familial and sporadic parasympathetic paragangliomas detected by comparative genomic hybridization

Parasympathetic paragangliomas (PGLs) represent neuroendocrine tumors arisi ng from chief cells in branchiomeric and intravagal paraganglia, which shar e several histological features with their sympathetic counterpart sympatho adrenal paragangliomas, In recent years, genetic analyses of the familial f orm of PGL have attracted considerable interest. However, the majority of p aragangliomas occurs sporadically and it remains to be determined whether t he pathogenesis of sporadic paraganglioma resembles that of the familial fo rm. Furthermore, data on comparative genetic aberrations are scarce. To pro vide fundamental cytogenetic data on sporadic and hereditary PGLs, we perfo rmed comparative genomic hybridization using directly fluorochrome-conjugat ed DNA extracted from 12 frozen and 4 paraffin-embedded tumors. The compara tive genomic hybridization data were extended by loss of heterozygosity ana lysis of chromosome 11q. DNA copy number changes were found in 10 (63%) of 16 tumors. The most frequent chromosomal imbalance involved loss of chromos ome 11. Six of seven familial tumors and two of nine sporadic tumors showed loss of 11q (86% versus 22%, P = 0.012). Deletions of 11p and 5p were foun d in two of nine sporadic tumors. We conclude that overall DNA copy number changes are infrequent in PGLs com pared to sympathetic paragangliomas and that loss of chromosome 11 may be an important event in their tumorigenesis , particularly in familial paragangliomas.