Genome-wide expression profiling reveals new insights into pathogenesis and progression of testicular germ cell tumors.
Testicular germ cell tumors (GCT) are the most frequent malignancy in young adults and arise from intratubular germ cell neoplasia undetermined (IGCNU, also referred to as carcinoma in situ, CIS). To determine the transcriptional programs involved in the transition from normal germ cells to GCT, and to further elucidate genetic differences between seminomas and non-seminomatous GCT the global expression profile of 12 neoplastic and 3 normal testicular tissues were investigated by whole genome cDNA microarrays. Transcriptional differences between seminomas and embryonal carcinomas were determined and gene signatures characterizing histological subtypes of GCT were identified. The most significant difference between seminomas and embryonal carcinomas was the expression of spermatogenesis-associated genes (PRAME, MAGEA4, SPAG1, HPX) in seminomas and regulatory genes DNMT3B and SOX2 as well as small molecular weight keratins KRT8, KRT18 in embryonal carcinomas. The expression of several selected genes (CK18, MAGE-A4, SOX2, DNMT3B, CD30, KIT) was studied by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR) in a large collective of GCT. In summary, our data identified tumor type-specific gene signatures of GCT and provided new insights into genetic pathways driving the transition to seminomas and embryonal carcinomas from their respective precursor lesions.
Biermann
Katharina
K
Department of Pathology, University of Bonn, Bonn, Germany. katharina.biermann@ukb.uni-bonn.de
Heukamp
Lukas Carl
LC
Steger
Klaus
K
Zhou
Hui
H
Franke
Folker Ernst
FE
Sonnack
Violetta
V
Brehm
Ralph
R
Berg
Johannes
J
Bastian
Patrick Jan
PJ
Muller
Stefan Cajetan
SC
Wang-Eckert
Lihua
L
Buettner
Reinhard
R
D000328:Adult; D018236:Carcinoma, Embryonal / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018239:Seminoma / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013736:Testicular Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology