TY - JOUR
T1 - Differential expression of SOX17 and SOX2 in germ cells and stem cells has biological and clinical implications
AU - de Jong, J
AU - Stoop, H
AU - Gillis, A J M
AU - van Gurp, R J H L M
AU - van de Geijn, G-J M
AU - Boer, M de
AU - Hersmus, R
AU - Saunders, P T K
AU - Anderson, R A
AU - Oosterhuis, J W
AU - Looijenga, L H J
PY - 2008/5
Y1 - 2008/5
N2 - Combined action of SOX and POU families of transcription factors plays major roles in embryonic development. In embryonic stem cells, the combination of SOX2 and POU5F1 (OCT3/4) is essential for maintaining the undifferentiated state by activating pluripotency-linked genes, and inhibition of genes involved in differentiation. Besides embryonic stem cells, POU5F1 is also present in early germ cells, primordial germ cells, and gonocytes, where it has a role in suppression of apoptosis. Here we demonstrate that SOX2 is absent in germ cells of human fetal gonads, and as expected carcinoma in situ (CIS), ie the precursor lesion of testicular germ cell tumours of adolescents and adults (TGCTs), and seminoma. Based on genome-wide expression profiling, SOX17 was found to be present, instead of SOX2, in early germ cells and their malignant counterparts, CIS and seminoma. Immunohistochemistry, western blot analysis, and quantitative RT-PCR showed that SOX17 is a suitable marker to distinguish seminoma from embryonal carcinoma, confirmed in representative cell lines. Aberrant SOX2 expression can be present in Sertoli cells when associated with CIS, which can be misdiagnosed as embryonal carcinoma. In conclusion, this study demonstrates the absence of SOX2 in human embryonic and malignant germ cells, which express SOX17 in conjunction with POU5F1. This finding has both diagnostic and developmental biological implications. It allows the identification of seminoma-like cells from embryonal carcinoma based on a positive marker and might be the explanation for the different function of POU5F1 in normal and malignant germ cells versus embryonic stem cells.
AB - Combined action of SOX and POU families of transcription factors plays major roles in embryonic development. In embryonic stem cells, the combination of SOX2 and POU5F1 (OCT3/4) is essential for maintaining the undifferentiated state by activating pluripotency-linked genes, and inhibition of genes involved in differentiation. Besides embryonic stem cells, POU5F1 is also present in early germ cells, primordial germ cells, and gonocytes, where it has a role in suppression of apoptosis. Here we demonstrate that SOX2 is absent in germ cells of human fetal gonads, and as expected carcinoma in situ (CIS), ie the precursor lesion of testicular germ cell tumours of adolescents and adults (TGCTs), and seminoma. Based on genome-wide expression profiling, SOX17 was found to be present, instead of SOX2, in early germ cells and their malignant counterparts, CIS and seminoma. Immunohistochemistry, western blot analysis, and quantitative RT-PCR showed that SOX17 is a suitable marker to distinguish seminoma from embryonal carcinoma, confirmed in representative cell lines. Aberrant SOX2 expression can be present in Sertoli cells when associated with CIS, which can be misdiagnosed as embryonal carcinoma. In conclusion, this study demonstrates the absence of SOX2 in human embryonic and malignant germ cells, which express SOX17 in conjunction with POU5F1. This finding has both diagnostic and developmental biological implications. It allows the identification of seminoma-like cells from embryonal carcinoma based on a positive marker and might be the explanation for the different function of POU5F1 in normal and malignant germ cells versus embryonic stem cells.
KW - Adult
KW - Biomarkers, Tumor/analysis
KW - Blotting, Western/methods
KW - Carcinoma in Situ/metabolism
KW - Cell Line
KW - Cell Line, Tumor
KW - DNA-Binding Proteins/genetics
KW - Female
KW - Gene Expression
KW - Gene Expression Profiling
KW - Germ Cells/metabolism
KW - Germinoma/metabolism
KW - HMGB Proteins/genetics
KW - High Mobility Group Proteins/genetics
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Octamer Transcription Factor-3/genetics
KW - Oligonucleotide Array Sequence Analysis
KW - Ovary/embryology
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - SOXB1 Transcription Factors
KW - SOXF Transcription Factors
KW - Seminoma/metabolism
KW - Stem Cells/metabolism
KW - Testicular Neoplasms/metabolism
KW - Testis/embryology
KW - Transcription Factors/genetics
UR - http://www.scopus.com/inward/record.url?scp=42949173880&partnerID=8YFLogxK
U2 - 10.1002/path.2332
DO - 10.1002/path.2332
M3 - Article
C2 - 18348160
SN - 0022-3417
VL - 215
SP - 21
EP - 30
JO - The Journal of pathology
JF - The Journal of pathology
IS - 1
ER -