title: Gene expression profiling of benign and malignant pheochromocytoma.
abstract: There are currently no reliable diagnostic and prognostic markers or effective treatments for malignant pheochromocytoma. This study used oligonucleotide microarrays to examine gene expression profiles in pheochromocytomas from 90 patients, including 20 with malignant tumors, the latter including metastases and primary tumors from which metastases developed. Other subgroups of tumors included those defined by tissue norepinephrine compared to epinephrine contents (i.e., noradrenergic versus adrenergic phenotypes), adrenal versus extra-adrenal locations, and presence of germline mutations of genes predisposing to the tumor. Correcting for the confounding influence of noradrenergic versus adrenergic catecholamine phenotype by the analysis of variance revealed a larger and more accurate number of genes that discriminated benign from malignant pheochromocytomas than when the confounding influence of catecholamine phenotype was not considered. Seventy percent of these genes were underexpressed in malignant compared to benign tumors. Similarly, 89% of genes were underexpressed in malignant primary tumors compared to benign tumors, suggesting that malignant potential is largely characterized by a less-differentiated pattern of gene expression. The present database of differentially expressed genes provides a unique resource for mapping the pathways leading to malignancy and for establishing new targets for treatment and diagnostic and prognostic markers of malignant disease. The database may also be useful for examining mechanisms of tumorigenesis and genotype-phenotype relationships. Further progress on the basis of this database can be made from follow-up confirmatory studies, application of bioinformatics approaches for data mining and pathway analyses, testing in pheochromocytoma cell culture and animal model systems, and retrospective and prospective studies of diagnostic markers.
authors.affiliation: Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, CRC, Room 1E-1-3140, 10 Center Drive, MSC-1109, Bethesda, MD 20892-1109, USA.
authors.forename: Frederieke M
authors.initials: FM
authors.lastname: Brouwers
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Munson
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barb
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
authors.forename: Ronald
authors.initials: R
authors.lastname: De Krijger
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.forename: Robert
authors.initials: R
authors.lastname: Udelsman
authors.forename: Idris T
authors.initials: IT
authors.lastname: Ocal
authors.forename: Barry L
authors.initials: BL
authors.lastname: Shulkin
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Jan
authors.initials: J
authors.lastname: Breza
authors.forename: Lucia
authors.initials: L
authors.lastname: Ksinantova
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010673:Pheochromocytoma / Q000235:genetics*