Deletion of 11q23 and cyclin D1 overexpression are frequent aberrations in parathyroid 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 P:RAD1/cyclin D1 gene and tumor suppressor gene loss have been described as genetic abnormalities in the evolution of parathyroid neoplasms. We studied tissue samples taken from primary parathyroid hyperplasia, parathyroid adenoma, and histologically normal parathyroid tissue by comparative genomic hybridization, fluorescent in situ hybridization, and immunohistochemistry for cyclin D1. DNA copy number changes were infrequent in primary hyperplasia (4 of 24, 17%), but common in adenomas (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 hyperplasias. Fluorescent in situ hybridization confirmed the presence of both MEN1 alleles located at 11q13 despite deletion of 11q23 in all three cases studied. Cyclin D1 was overexpressed in six (40%) of the 15 adenomas studied, whereas none of the 27 hyperplasias (P: = 0.0010) nor the five histologically normal tissue samples overexpressed cyclin D1. Either DNA copy number loss or cyclin D1 overexpression was present in 13 (81%) of the 16 adenomas. We conclude that DNA copy number loss and cyclin D1 overexpression are common in parathyroid adenomas. The region 11q23 is frequently lost in parathyroid adenomas and occasionally in parathyroid hyperplasias, and this suggests the possibility that a tumor suppressor gene that is important in their pathogenesis is present on 11q23.
Hemmer
S
S
Department of Oncology, Laboratory of Medical Genetics, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00029 HYKS, Helsinki, Finland.
Wasenius
V M
VM
Haglund
C
C
Zhu
Y
Y
Knuutila
S
S
Franssila
K
K
Joensuu
H
H
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002880:Chromosomes, Human, Pair 11; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000378:metabolism*
D019938:Cyclin D1