Chromosome 11 genomic changes in parathyroid adenoma and hyperplasia: array CGH, FISH, and tissue microarrays.
We have used a combination of gene expression profiling, array comparative genomic hybridization (aCGH), fluorescent in situ hybridization (FISH) and tissue microarrays (TMAs) to investigate chromosome 11 genetic changes in subsets of benign parathyroid tumors. Integration of gene expression profiling and aCGH was done using differential gene locus mapping analysis. We have identified three distinct relatively common chromosome 11 genomic changes in various subsets of parathyroid tumors. The simplest and least common of these genomic changes involves translocation of the CCND1 gene with subsequent strong CCND1 expression. This genetic change is essentially limited to parathyroid adenomas (8%), although expression of CCND1 without translocation is common in uremic hyperparathyroidism. Not surprisingly, deletion of the MEN1 locus at 11q13 or loss of a large portion or an entire chromosome 11 was a common finding. This particular genomic change appears to have a prominent effect on the overall results of gene expression profiling and was present in slightly less than one-half of adenomas. Genomic changes in primary nonfamilial hyperplasia were for the most part restricted to 11q13 deletion or loss of chromosome 11. The third genomic change we identified was 11q23 deletion. This genetic change was relatively independent of other chromosome 11 changes and present in slightly less than one-half of adenomas. 11q23 deletion along with relatively strong CCND1 expression was common in uremic hyperparathyroidism.
Yi
Y
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Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Nowak
Norma J
NJ
Pacchia
Annmarie L
AL
Morrison
Carl
C
D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics*; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics; D023281:Genomics / Q000379:methods*; D006801:Humans; D006965:Hyperplasia / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D010282:Parathyroid Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D046888:Tissue Array Analysis
D056741:Cyclin D; D016213:Cyclins; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins