Gene Expression Profiling Differentiates Germ Cell Tumors from Other Cancers and Defines Subtype-Specific Signatures

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 express...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-12, Vol.102 (49), p.17763-17768
Main Authors: Dejan Juric, Sanja Sale, Hromas, Robert A., Ron Yu, Wang, Yan, George E. Duran, Tibshirani, Robert, Einhorn, Lawrence H., Sikic, Branimir I.
Format: Article
Language:English
Subjects:
Biological Sciences
Cells
Chromosomes, Human - genetics
Embryonic stem cells
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes
Germ cells
Histology
Humans
Male
Medical research
Mesonephroma
Neoplasms - classification
Neoplasms - genetics
Neoplasms, Germ Cell and Embryonal - classification
Neoplasms, Germ Cell and Embryonal - genetics
Neoplasms, Germ Cell and Embryonal - pathology
Seminoma
Signatures
Teratoma
Testicular cancer
Tumors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0509082102