Wruck, W;
Bremmer, F;
Kotthoff, M;
Fichtner, A;
Skowron, MA;
Schönberger, S;
Calaminus, G;
... Nettersheim, D; + view all
(2021)
The pioneer and differentiation factor FOXA2 is a key driver of yolk-sac tumour formation and a new biomarker for paediatric and adult yolk-sac tumours.
Journal of Cellular and Molecular Medicine
, 25
(3)
pp. 1394-1405.
10.1111/jcmm.16222.
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The pioneer and differentiation factor FOXA2 is a key driver of yolk-sac tumour formation and a new biomarker for paediatric.pdf - Published Version Download (2MB) | Preview |
Abstract
Yolk-sac tumours (YSTs), a germ cell tumour subtype, occur in newborns and infants as well as in young adults of age 14-44 years. In clinics, adult patients with YSTs face a poor prognosis, as these tumours are often therapy-resistant and count for many germ cell tumour related deaths. So far, the molecular and (epi)genetic mechanisms that control development of YST are far from being understood. We deciphered the molecular and (epi)genetic mechanisms regulating YST formation by meta-analysing high-throughput data of gene and microRNA expression, DNA methylation and mutational burden. We validated our findings by qRT-PCR and immunohistochemical analyses of paediatric and adult YSTs. On a molecular level, paediatric and adult YSTs were nearly indistinguishable, but were considerably different from embryonal carcinomas, the stem cell precursor of YSTs. We identified FOXA2 as a putative key driver of YST formation, subsequently inducing AFP, GPC3, APOA1/APOB, ALB and GATA3/4/6 expression. In YSTs, WNT-, BMP- and MAPK signalling-related genes were up-regulated, while pluripotency- and (primordial) germ cell-associated genes were down-regulated. Expression of FOXA2 and related key factors seems to be regulated by DNA methylation, histone methylation / acetylation and microRNAs. Additionally, our results highlight FOXA2 as a promising new biomarker for paediatric and adult YSTs.
| Type: | Article |
|---|---|
| Title: | The pioneer and differentiation factor FOXA2 is a key driver of yolk-sac tumour formation and a new biomarker for paediatric and adult yolk-sac tumours |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/jcmm.16222 |
| Publisher version: | https://doi.org/10.1111/jcmm.16222 |
| Language: | English |
| Additional information: | © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Adult and paediatric germ cell tumours, biomarker, DNA methylation, embryonal carcinomas, FOXA2, microRNA, Pluripotency, SOX17, Yolk-sac tumours |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10179443 |
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