Open AccessGene expression profiling differentiates germ cell tumors from other cancers and defines subtype-specific signatures
Author(s) -
Dejan Juric,
Sanja Šale,
Robert Hromas,
Ronald Yu,
Yan Wang,
George E. Durán,
Robert Tibshirani,
Lawrence H. Einhorn,
Branimir I. Šikić
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0509082102
Subject(s) - biology , gene expression profiling , germ cell tumors , cancer research , cell cycle , gene , gene expression , yolk sac , seminoma , germ cell , pathology , genetics , medicine , embryo , chemotherapy
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 , andKIT ). Several additional differentially expressed genes were identified in teratomas (EGR1 andMMP7 ), yolk sac tumors (PTPN13 andFN1 ), and seminomas (NR6A1 ,DPPA4 , andIRX1 ). 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.