Gene Expression Profiling of PDGFRA Mutant GIST Reveals Immune Signatures as a Specific Fingerprint of D842V Exon 18 Mutation.

Frontiers in Immunology
Valentina IndioMargherita Nannini

Abstract

Platelet Derived Growth Factor Receptor Alpha (PDGFRA) mutations occur in only about 5-7% of gastrointestinal stromal tumors (GIST), notably with alterations on exons 12/14/18. The most frequent PDGFRA mutation is the exon 18 D842V, which is correlated to specific clinico-pathological features, such as primary imatinib resistance and higher indolence. Here, we present a gene expression profile (GEP) comparison of D842V vs. PDGFRA with mutations other than D842V (non-D842V). GEP was followed by in silico bioinformatic analysis aimed at evaluating differential expression, tumor microenvironment composition and pathway enrichment. We found a large set of oncogenes, transcription factors and nuclear receptors downregulated in the D842V mutant. Conversely, D842V showed a significant enrichment of immune- and interferon- related gene signatures. Differences in tumor microenvironment composition were also highlighted, including a higher abundance of CD8+ T-cells and an overexpression of the T cell-inflamed signature in the D842V mutant subgroup, which is predictive of immunotherapy response. PDGFRA D842V vs. non-D842V GIST display a different expression profile, with a prominent immunological signature, that could represent a proof of...Continue Reading

References

Jan 11, 2003·Science·Michael C HeinrichJonathan A Fletcher
Dec 4, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael C HeinrichJonathan A Fletcher
Mar 11, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M Debiec-RychterUNKNOWN EORTC Soft Tissue and Bone Sarcoma Group
May 18, 2004·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jerzy LasotaMarkku Miettinen
Jun 2, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christopher L CorlessMichael C Heinrich
Oct 29, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael C HeinrichGeorge D Demetri
Jun 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Philippe A CassierUNKNOWN European Organisation for Research and Treatment of Cancer
Jun 30, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael C HeinrichMaria Debiec-Rychter
Dec 11, 2013·The Journal of Experimental Medicine·Michael J CavnarRonald P DeMatteo
Oct 9, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Agnieszka WozniakMaria Debiec-Rychter
Jul 2, 2015·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Changhoon YooYoon-Koo Kang
Jul 30, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adrian M SeifertRonald P DeMatteo
Jun 27, 2017·The Journal of Clinical Investigation·Mark AyersTerrill K McClanahan
Mar 8, 2018·International Journal of Molecular Sciences·Valentina IndioMaria Aabbondanza Pantaleo
Oct 3, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yemarshet K GebreyohannesPatrick Schöffski
Feb 15, 2019·The Journal of Clinical Investigation·Gerardo A VitielloRonald P DeMatteo

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Citations

Feb 13, 2021·Cancers·Alessandro RizzoMargherita Nannini
Jan 10, 2021·International Journal of Molecular Sciences·Christos VallilasMichalis V Karamouzis
Apr 4, 2021·Journal of Clinical Medicine·Valentina IndioMaria Abbondanza Pantaleo
Jul 25, 2021·International Journal of Molecular Sciences·Marcella TazzariViviana Vallacchi

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Methods Mentioned

BETA
chip
PCR

Software Mentioned

rgl
limma
R
Gene Set Enrichment Analysis ( GSEA )
pheatmap
oligo
bioconductor
CIBERSORT
bioconductor package
REACTOME

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