Gene duplication, rather than epigenetic changes, drives FGF4 overexpression in KIT/PDGFRA/SDH/RAS-P WT GIST.

Scientific Reports
Milena UrbiniMaria Abbondanza Pantaleo

Abstract

Gastrointestinal stromal tumours that are wild type for KIT and PDGFRA are referred to as WT GISTs. Of these tumours, SDH-deficient (characterized by the loss of SDHB) and quadruple WT GIST (KIT/PDGFRA/SDH/RAS-P WT) subgroups were reported to display a marked overexpression of FGF4, identifying a putative common therapeutic target for the first time. In SDH-deficient GISTs, methylation of an FGF insulator region was found to be responsible for the induction of FGF4 expression. In quadruple WT, recurrent focal duplication of FGF3/FGF4 was reported; however, how it induced FGF4 expression was not investigated. To assess whether overexpression of FGF4 in quadruple WT could be driven by similar epigenetic mechanisms as in SDH-deficient GISTs, we performed global and locus-specific (on FGF4 and FGF insulator) methylation analyses. However, no epigenetic alterations were detected. Conversely, we demonstrated that in quadruple WT GISTs, FGF4 expression and the structure of the duplication were intimately connected, with the copy of FGF4 closer to the ANO1 super-enhancer being preferentially expressed. In conclusion, we demonstrated that in quadruple WT GISTs, FGF4 overexpression is not due to an epigenetic mechanism but rather to the ...Continue Reading

References

Sep 15, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christopher L CorlessMichael C Heinrich
Mar 23, 2010·The American Journal of Surgical Pathology·Anthony J GillRoderick J Clifton-Bligh
Aug 15, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A AdenisA Le Cesne
Jun 4, 2016·Molecular Cell·Jesse R DixonBing Ren
Dec 16, 2016·Journal of Translational Medicine·Eileen ShiJason K Sicklick
Aug 30, 2017·British Journal of Cancer·Heikki JoensuuAxel Le Cesne
Mar 20, 2019·Genes, Chromosomes & Cancer·Milena UrbiniMaria Abbondanza Pantaleo
Oct 17, 2019·Nature·William A FlavahanBradley E Bernstein
Nov 2, 2019·Nature·William A FlavahanBradley E Bernstein
Sep 1, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A AdenisA Le Cesne
Feb 7, 2020·Nature Genetics·Kadir C AkdemirUNKNOWN PCAWG Consortium
May 13, 2020·International Journal of Molecular Sciences·Annalisa AstolfiMargherita Nannini

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Citations

Apr 4, 2021·Journal of Clinical Medicine·Valentina IndioMaria Abbondanza Pantaleo

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Methods Mentioned

BETA
PCR
RNA-seq

Clinical Trials Mentioned

NCT02638766

Software Mentioned

FusionMap
Defuse
ChimeraScan

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