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MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven

Jolien De Wyn1, Mark W Zimmerman2, Nina Weichert-Leahey2

  • 1Department for Biomolecular Medicine, Ghent University, Medical Research Building (MRB1), Corneel Heymanslaan 10, B-9000 Ghent, Belgium.

Cancers
|October 13, 2021
PubMed

Insights

Researchers identified key factors like MEIS2 and ASCL1 driving neuroblastoma formation in MYCN-amplified tumors. This study reveals novel therapeutic targets for this aggressive pediatric cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MYCN amplification is present in about half of high-risk neuroblastoma patients.
  • The early steps of MYCN-driven neuroblastoma initiation remain poorly understood.
  • Understanding these early events is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the molecular landscape of early neuroblastoma development in a MYCN-driven model.
  • To identify novel factors involved in tumor initiation and maintenance.
  • To discover potential therapeutic targets for MYCN-driven neuroblastoma.

Main Methods:

  • Performed time-resolved transcriptome analysis in a murine TH-MYCN neuroblastoma model.
  • Utilized bioinformatics to identify candidate tumor-initiating factors and regulatory circuits.
  • Conducted cross-species master regulator analysis to identify key transcriptional hubs.

Main Results:

  • Identified MEIS2 and ASCL1 as potential tumor-initiating factors in adrenergic neuroblastomas.
  • Found upregulation of KEOPS complex member (gm6890), Claspin (CLSPN), and chromosome 17q loci (CBX2, GJC1, LIMD2) during tumor formation.
  • FOXM1 identified as a master regulator controlling transcriptome profiles in MYCN-driven neuroblastoma.

Conclusions:

  • Time-resolved transcriptome analysis revealed novel components in early neuroblastoma lesions and established tumors.
  • These findings implicate new factors in both the initiation and maintenance of MYCN-driven neuroblastoma.
  • Identified putative novel drug targets for therapeutic intervention in MYCN-driven neuroblastoma.
Keywords:
MYCNmouse modelneuroblastomatranscriptome analysis

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