Cripto: expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors

Spiller, Cassy M., Gillis, Ad J. M., Burnet, Guillaume, Stoop, Hans, Koopman, Peter, Bowles, Josephine and Looijenga, Leendert H. J. (2016) Cripto: expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors. Molecular Oncology, 10 4: 526-537. doi:10.1016/j.molonc.2015.11.003

Author Spiller, Cassy M.
Gillis, Ad J. M.
Burnet, Guillaume
Stoop, Hans
Koopman, Peter
Bowles, Josephine
Looijenga, Leendert H. J.
Title Cripto: expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors
Journal name Molecular Oncology   Check publisher's open access policy
ISSN 1574-7891
Publication date 2016-04-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.molonc.2015.11.003
Open Access Status DOI
Volume 10
Issue 4
Start page 526
End page 537
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 1313 Molecular Medicine
1311 Genetics
1306 Cancer Research
Abstract Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co-receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non-seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non-seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Keyword Cripto
Testicular germ cell cancer
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1030146
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Sat, 02 Apr 2016, 02:02:05 EST by Susan Allen on behalf of Institute for Molecular Bioscience