Distinction in gene expression profiles demonstrated in parathyroid adenomas by high-density oligoarray technology.
OBJECTIVE
Somatic deletion of chromosome 11q13 is the most frequent genetic aberration in parathyroid adenoma. To gain further insight into the genetic etiology of parathyroid tumor development, we examined a comprehensive gene expression profile of parathyroid adenomas and normal parathyroid tissues. The results were then evaluated with respect to differences between adenomas and normal parathyroid tissue, and to the presence of loss of heterozygosity (LOH) in chromosomal region 11q13.


METHODS
Sporadic parathyroid adenomas and normal parathyroids were hybridized against HG-U95Av2 oligonucleotide arrays (Affymetrix) containing a total of 12,625 probe sets. Quantitative real-time PCR (QRT-PCR) was performed in a larger series of parathyroid adenomas, in order to con-firm the microarray results.


RESULTS
Cyclin D1 and c-Jun showed increased expression in adenomas vs normal parathyroids by microarray analysis and QRT-PCR, suggesting an oncogenic role of these genes in parathyroid tumor development. At unsupervised hierarchical clustering, the adenomas fell into two groups: Group I adenomas were characterized by 11q13 LOH, while Group II adenomas lacked this abnormality. In addition, a t-test analysis identified largely non-overlapping genes with differential expression in the tumors subgroups; e.g. in Group I tumors the putative oncogene ENC 1 was found highly over-expressed vs Group II adenomas.


CONCLUSIONS
The microarray analyses revealed partly distinctive and partly common expression profiles in parathyroid adenomas with and without 11q13 LOH. In addition, approximately half of the under-expressed genes were mapped to chromosome 11, in agreement with a dose effect following loss of this chromosome.
Forsberg
Lars
L
Department of Molecular Medicine, Karolinska University Hospital CMM L8:01, SE-17176 Stockholm, Sweden.
Björck
Erik
E
Hashemi
Jamileh
J
Zedenius
Jan
J
Höög
Anders
A
Farnebo
Lars-Ove
LO
Reimers
Mark
M
Larsson
Catharina
C
D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D016758:Genes, jun; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D005810:Multigene Family; D010282:Parathyroid Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019938:Cyclin D1