title: Gene expression profiling differentiates germ cell tumors from other cancers and defines subtype-specific signatures.
abstract: Germ cell tumors (GCTs) of the testis are the predominant cancer among young men. We analyzed gene expression profiles of 50 GCTs of various subtypes, and we compared them with 443 other common malignant tumors of epithelial, mesenchymal, and lymphoid origins. Significant differences in gene expression were found among major histological subtypes of GCTs, and between them and other malignancies. We identified 511 genes, belonging to several critical functional groups such as cell cycle progression, cell proliferation, and apoptosis, to be significantly differentially expressed in GCTs compared with other tumor types. Sixty-five genes were sufficient for the construction of a GCT class predictor of high predictive accuracy (100% training set, 96% test set), which might be useful in the diagnosis of tumors of unknown primary origin. Previously described diagnostic and prognostic markers were found to be expressed by the appropriate GCT subtype (AFP, POU5F1, POV1, CCND2, and KIT). Several additional differentially expressed genes were identified in teratomas (EGR1 and MMP7), yolk sac tumors (PTPN13 and FN1), and seminomas (NR6A1, DPPA4, and IRX1). Dynamic computation of interaction networks and mapping to existing pathways knowledge databases revealed a potential role of EGR1 in p21-induced cell cycle arrest and intrinsic chemotherapy resistance of mature teratomas.
authors.affiliation: Oncology Division, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5151, USA.
authors.forename: Dejan
authors.initials: D
authors.lastname: Juric
authors.forename: Sanja
authors.initials: S
authors.lastname: Sale
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hromas
authors.forename: Ron
authors.initials: R
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: George E
authors.initials: GE
authors.lastname: Duran
authors.forename: Robert
authors.initials: R
authors.lastname: Tibshirani
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Einhorn
authors.forename: Branimir I
authors.initials: BI
authors.lastname: Sikic
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000145:classification* / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000145:classification* / Q000235:genetics* / Q000473:pathology