Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling.

Abstract:

:Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.

journal_name

Cancer Res

journal_title

Cancer research

authors

Almstrup K,Hoei-Hansen CE,Wirkner U,Blake J,Schwager C,Ansorge W,Nielsen JE,Skakkebaek NE,Rajpert-De Meyts E,Leffers H

doi

10.1158/0008-5472.CAN-04-0679

subject

Has Abstract

pub_date

2004-07-15 00:00:00

pages

4736-43

issue

14

eissn

0008-5472

issn

1538-7445

pii

64/14/4736

journal_volume

64

pub_type

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