FREQUENT LOSS OF CHROMOSOME ARM IP DNA IN PARATHYROID ADENOMAS

Two molecular defects have been described in parathyroid adenomas: rea rrangement and overexpression of the PRADI/cyclin DI oncogene and alle lic loss of chromosome II DNA, often including the multiple endocrine neoplasia type 1 (MENI) putative tumor suppressor gene region. In an e ffort to identify additional parathyroid tumor suppressor genes, we ex amined 25 parathyroid adenomas for tumor-specific allelic loss of poly morphic DNA loci located near known or candidate tumor suppressor gene s. Control leukocyte DNA from all 25 patients was heterozygous for 1 o r more of the 9 chromosome markers examined. Allelic loss at 1 or more of these informative loci on chromosome was observed in 10 of 25 (40% ) adenomas. Although many tumors lost extensive regions on chromosome I, all but one of these tumors had allelic loss of distal Ip (Ip32-pte r); four tumors also lost loci on Iq. Allelic loss at IIq13, the site of the MENI gene, was detected in 5 of 21 (24%) informative cases, inc luding 3 with Ip loss. In contrast, allelic loss was rarely observed a t loci on 9q and 10p and was not observed at loci on 3p, 3q, 4p, 5q, 1 2q, 14q, 18q, 22q, or Xp. In summary, clonal allelic loss of loci on c hromosome arm Ip is a frequent feature of parathyroid adenomas, implyi ng that inactivation of a tumor suppressor gene(s) on Ip commonly cont ributes to their pathogenesis. (C) 1995 Wiley-Liss, Inc.