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.
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 humantumors 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 humanNANOG 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.
Authors: Timothy M Pierpont; Amy M Lyndaker; Claire M Anderson; Qiming Jin; Elizabeth S Moore; Jamie L Roden; Alicia Braxton; Lina Bagepalli; Nandita Kataria; Hilary Zhaoxu Hu; Jason Garness; Matthew S Cook; Blanche Capel; Donald H Schlafer; Teresa Southard; Robert S Weiss Journal: Cell Rep Date: 2017-11-14 Impact factor: 9.423