FREQUENT LOSS OF CHROMOSOME ARM IP DNA IN PARATHYROID ADENOMAS

Two molecular defects have been described in parathyroid adenomas: rearrangement and overexpression of the PRADI/cyclin DI oncogene and allelic loss of chromosome II DNA, often including the multiple endocrine neoplasia type 1 (MENI) putative tumor suppressor gene region. In an effort to identify additional parathyroid tumor suppressor genes, we examined 25 parathyroid adenomas for tumor-specific allelic loss of polymorphic DNA loci located near known or candidate tumor suppressor genes. Control leukocyte DNA from all 25 patients was heterozygous for 1 or 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-pter); 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, including 3 with Ip loss. In contrast, allelic loss was rarely observed at loci on 9q and 10p and was not observed at loci on 3p, 3q, 4p, 5q, 12q, 14q, 18q, 22q, or Xp. In summary, clonal allelic loss of loci on chromosome arm Ip is a frequent feature of parathyroid adenomas, implying that inactivation of a tumor suppressor gene(s) on Ip commonly contributes to their pathogenesis. (C) 1995 Wiley-Liss, Inc.