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.
DNA methylation
FOXA2
Pluripotency
SOX17
Yolk-sac tumours
adult and paediatric germ cell tumours
biomarker
embryonal carcinomas
microRNA
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
15
09
2020
revised:
04
12
2020
accepted:
08
12
2020
pubmed:
16
1
2021
medline:
23
9
2021
entrez:
15
1
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33448076
doi: 10.1111/jcmm.16222
pmc: PMC7875904
doi:
Substances chimiques
Biomarkers, Tumor
0
FOXA2 protein, human
0
Oncogene Proteins
0
Hepatocyte Nuclear Factor 3-beta
135845-92-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1394-1405Subventions
Organisme : CIO-ABCD
Organisme : Wilhelm Sander-Stiftung
ID : 2016.041.1/2016.041.2
Informations de copyright
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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