Gene expression profiling differentiates germ cell tumors from other cancers and defines subtype-specific signatures

Dejan Juric, Sanja Sale, Robert A. Hromas, Ron Yu, Yan Wang, George E. Duran, Robert Tibshirani, Lawrence H. Einhorn, Branimir I. Sikic

Research output: Contribution to journalArticle

53 Scopus citations

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 (PTPNT3 and FN1), and seminomas (NR6A1, DPPA4, and JRX1). 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.

Original languageEnglish (US)
Pages (from-to)17763-17768
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number49
DOIs
StatePublished - Dec 6 2005

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Keywords

  • DNA microarrays
  • Molecular interaction networks
  • Testicular cancer
  • Unknown primary tumors

ASJC Scopus subject areas

  • Genetics
  • General

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