Deletion of 11q23 and cyclin D1 overexpression are frequent aberrations inparathyroid adenomas

Hyperparathyroidism may result from parathyroid hyperplasia or adenoma, or rarely from parathyroid carcinoma. Pericentromeric inversion of chromosome 11 that results in activation of the PRAD1/cyclin DI gene and tumor suppres sor gene loss have been described as genetic abnormalities in the evolution of parathyroid neoplasms. We studied tissue samples taken from primary par athyroid hyperplasia, parathyroid adenoma, and histologically normal parath yroid tissue by comparative genomic hybridization, fluorescent in situ hybr idization, and immunohistochemistry for cyclin D1. DNA copy number changes were infrequent in primary hyperplasia (4 of 24, 17%), but common in adenom as (10 of 16, 63%; P = 0.0059). The most common change was deletion of the entire chromosome 11 or a part of it, with a minimal common region at 11q23 , This change was present in five (31%) adenomas and two (8%) primary hyper plasias. Fluorescent in situ hybridization confirmed the presence of both M EN1 alleles located at 11q13 despite deletion of 11q23 in ah three cases st udied Cyclin D1 was overexpressed in six (40%) of the 15 adenomas studied, whereas none of the 27 hyperplasias (P = 0.0010) nor the five histologicall y normal tissue samples overexpressed cyclin D1, Either DNA copy number los s or cyclin D1 overexpression was present in 13 (81%) of the 16 adenomas, W e conclude that DNA copy number loss and cyclin D1 overexpression are commo n in parathyroid adenomas. The region 11q23 is frequently lost in parathyro id adenomas and occasionally in parathyroid hyperplasias, and this suggests the possibility that a tumor suppressor gene that is important in their pa thogenesis is present on 11q23.