Differentially Methylated Regions in Desmoid-Type Fibromatosis: A Comparison Between CTNNB1 S45F and T41A Tumors

Frontiers in Oncology
Milea J M TimbergenErik A C Wiemer

Abstract

The majority of desmoid-type fibromatosis (DTF) tumors harbor a β-catenin mutation, affecting specific codons in CTNNB1 exon 3. S45F tumors are reported to have a higher chance of recurrence after surgery and more resistance to systemic treatments compared to wild-type (WT) and T41A tumors. The aim of this pilot study was to examine the genome-wide DNA methylation profiles of S45F and T41A mutated DTF, to explain the observed differences in clinical behavior between these DTF subtypes. Genome-wide analysis of DNA methylation was performed using MeD-seq on formalin-fixed, paraffin-embedded primary DTF samples harboring a S45F (n = 14) or a T41A (n = 15) mutation. Differentially methylated regions (DMRs) between S45F and T41A DTF were identified and used for a supervised hierarchical cluster analysis. DMRs with a fold-change ≥1.5 were considered to be differentially methylated and differences between S45F and T41A tumors were quantitatively assessed. The effect of DMRs on the expression of associated genes was assessed using an independent mRNA expression dataset. Protein-protein interactions between WT β-catenin and mutant variants and DNA methyltransferase 1 (DNMT1) were examined by immunoprecipitation experiments. MeD-seq anal...Continue Reading

References

Apr 19, 2003·Science·François GaudetRudolf Jaenisch
Sep 18, 2004·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Tony L NgTorsten O Nielsen
May 9, 2008·Nature Reviews. Genetics·Miho M Suzuki, Adrian Bird
Oct 4, 2008·The American Journal of Pathology·Alexander J F LazarDina Lev
Mar 24, 2009·Nature Reviews. Molecular Cell Biology·Christian MosimannKonrad Basler
Sep 16, 2010·Cancer Research·Colleen WuBenjamin A Alman
Apr 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sébastien SalasFrederic Chibon
Dec 22, 2015·Cancer Medicine·Shunsuke HamadaYoshihiro Nishida
Feb 10, 2016·Acta Neuropathologica·Manuel RöhrichDavid E Reuss
Jun 4, 2016·Cancer Research·Michael KlutsteinHoward Cedar
Nov 4, 2016·Epigenomics·Pei LiuZhenfeng Duan
Jan 31, 2017·Nature Medicine·Nathan C SheffieldEleni M Tomazou
Jul 29, 2017·Clinical and Experimental Medicine·Yunbao PanYirong Li
Nov 3, 2017·Cancer Research·James T RobinsonJill P Mesirov
Jan 14, 2018·Scientific Reports·Kelly A MercierBenjamin Alman
Feb 23, 2019·Chronobiology International·Inês ChavesGijsbertus T J van der Horst
Apr 14, 2019·Cancer·Danielle BraggioRaphael E Pollock
Dec 6, 2019·Frontiers in Genetics·Warwick J LockeJason P Ross
Dec 18, 2019·Essays in Biochemistry·Ksenia SkvortsovaPhillippa Taberlay

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Datasets Mentioned

BETA
PRJNA604749
GSE58697

Methods Mentioned

BETA
MeD-seq
DNA-seq
transfections
transfection
scraping
immunoprecipitation
surgical resection

Software Mentioned

Python
bcl2fastq
Integrative Genomics Viewer ( IGV )
SPSS Statistics
MeD
bowtie2
Hg

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