NOVEL CHROMOSOMAL-ABNORMALITIES IDENTIFIED BY COMPARATIVE GENOMIC HYBRIDIZATION IN PARATHYROID ADENOMAS

The molecular basis of parathyroid adenomatosis includes defects in th e cyclin D1/PRAD1 and MEN1 genes but is, in large part, unknown. To id entify new locations of parathyroid oncogenes or tumor suppressor gene s, and to further establish the importance of DNA losses described by molecular allelotyping, we performed comparative genomic hybridization (CGH) on a panel of 53 typical sporadic (nonfamilial) parathyroid ade nomas. CGH is a new molecular cytogenetic technique in which the entir e tumor genome is screened for chromosomal gains and/or losses. Two ab normalities, not previously described, were found recurrently: gain of chromosome 16p (6 of 53 tumors, or 11%) and gain of chromosome 19p (5 of 53, or 9%). Losses were found frequently on 11p (14 of 53, or 26%) , as well as 11q (18 of 53, or 34%). Recurrent losses were also seen o n chromosomes 1p, 1q, 6q, 9p, 9q, 13q, and 15q, with frequencies rangi ng from 8-19%. Twenty-four of the 53 adenomas were also extensively an alyzed with polymorphic microsatellite markers for allelic losses, eit her in this study (11 cases) or previously (13 cases). Molecular allel otyping results were highly concordant with CGH results in these tumor s (concordance level of 97.5% for all informative markers/chromosome a rms examined). In conclusion, CGH has identified the first two known c hromosomal gain defects in parathyroid adenomas, suggesting the existe nce of direct-acting parathyroid oncogenes on chromosomes 16 and 19. C GH has confirmed the locations of putative parathyroid tumor suppresso r genes, also defined by molecular allelotyping, on chromosomes 1p, 6q , 9p, 11q, 13q, and 15q. Finally, CGH has provided new evidence favori ng the possibility that distinct parathyroid tumor suppressors exist o n 1p and 1q, and has raised the possibility of a parathyroid tumor sup pressor gene on 11p, distinct from the MEN1 gene on 11q. CGH can ident ify recurrent genetic abnormalities in hyperparathyroidism, especially chromosomal gains, that other methods do not detect.