title: Gene expression of parathyroid tumors: molecular subclassification and identification of the potential malignant phenotype.
abstract: Parathyroid tumors are heterogeneous, and diagnosis is often difficult using histologic and clinical features. We have undertaken expression profiling of 53 hereditary and sporadic parathyroid tumors to better define the molecular genetics of parathyroid tumors. A class discovery approach identified three distinct groups: (1) predominantly hyperplasia cluster, (2) HRPT2/carcinoma cluster consisting of sporadic carcinomas and benign and malignant tumors from Hyperparathyroidism-Jaw Tumor Syndrome patients, and (3) adenoma cluster consisting mainly of primary adenoma and MEN 1 tumors. Gene sets able to distinguish between the groups were identified and may serve as diagnostic biomarkers. We demonstrated, by both gene and protein expression, that Histone 1 Family 2, amyloid beta precursor protein, and E-cadherin are useful markers for parathyroid carcinoma and suggest that the presence of a HRPT2 mutation, whether germ-line or somatic, strongly influences the expression pattern of these 3 genes. Cluster 2, characterized by HRPT2 mutations, was the most striking, suggesting that parathyroid tumors with somatic HRPT2 mutation or tumors developing on a background of germ-line HRPT2 mutation follow pathways distinct from those involved in mutant MEN 1-related parathyroid tumors. Furthermore, our findings likely preclude an adenoma to carcinoma progression model for parathyroid tumorigenesis outside of the presence of either a germ-line or somatic HRPT2 mutation. These findings provide insights into the molecular pathways involved in parathyroid tumorigenesis and will contribute to a better understanding, diagnosis, and treatment of parathyroid tumors.
authors.affiliation: Laboratory of Cancer Genetics and Bioinformatics Special Program, Van Andel Research Institute, Grand Rapids, Michigan, USA.
authors.forename: Carola J
authors.initials: CJ
authors.lastname: Haven
authors.forename: Viive M
authors.initials: VM
authors.lastname: Howell
authors.forename: Paul H C
authors.initials: PH
authors.lastname: Eilers
authors.forename: Robert
authors.initials: R
authors.lastname: Dunne
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Marjo
authors.initials: M
authors.lastname: van Puijenbroek
authors.forename: Kyle
authors.initials: K
authors.lastname: Furge
authors.forename: Job
authors.initials: J
authors.lastname: Kievit
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Leigh W
authors.initials: LW
authors.lastname: Delbridge
authors.forename: Jeanette
authors.initials: J
authors.lastname: Philips
authors.forename: Anne E
authors.initials: AE
authors.lastname: Nelson
authors.forename: Ulf
authors.initials: U
authors.lastname: Krause
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Cuong
authors.initials: C
authors.lastname: Hoang-Vu
authors.forename: Oliver
authors.initials: O
authors.lastname: Gimm
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: Bin T
authors.initials: BT
authors.lastname: Teh
mesh_terms: D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010282:Parathyroid Neoplasms / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015854:Up-Regulation
chemical_list: C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins