The pluripotency homeobox gene NANOG is expressed in human germ cell tumors.
BACKGROUND
The NANOG gene, a member of the homeobox family of DNA binding transcription factors, was recently identified in a screen for pluripotency-promoting genes. NANOG overexpression in murine embryonic stem cells is sufficient to maintain self-renewal and to block differentiation. The NANOG gene is located on human chromosome 12p13, a region frequently duplicated in human tumors of germ cell origin and in cultured human embryonic stem cells. Here we investigate the expression and gene copy number of NANOG in human germ cells and tumors of germ cell origin.


METHODS
Immunohistochemistry and quantitative polymerase chain reaction (QPCR) were used to examine the expression and gene copy number of the human NANOG gene in germ cell tumors.


RESULTS
NANOG protein was detected in germline stem cells (gonocytes) within the developing testis. Immunohistochemistry and quantitative real-time PCR analysis were used to demonstrate that NANOG is highly and specifically expressed in carcinoma in situ (CIS), embryonal carcinomas, and seminomas, but not in teratomas and yolk sac tumors.


CONCLUSIONS
NANOG expression in germline stem cells (gonocytes), CIS, embryonal carcinoma, and seminoma reveals a molecular and developmental link between germ cell tumors and the embryonic cells from which they arise. Identification of NANOG as a molecular marker of undifferentiated germ cell tumors provides a novel tool for identifying and classifying tumors of germ cell origin.
Hart
Adam H
AH
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. hart@wehi.edu.au
Hartley
Lynne
L
Parker
Karen
K
Ibrahim
Marilyn
M
Looijenga
Leendert H J
LH
Pauchnik
Marija
M
Chow
Chung Wo
CW
Robb
Lorraine
L
D014408:Biomarkers, Tumor / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005333:Fetus; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D000071317:Nanog Homeobox Protein; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013094:Spermatozoa / Q000378:metabolism*; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human