AUTHOR=Indio Valentina , Ravegnini Gloria , Astolfi Annalisa , Urbini Milena , Saponara Maristella , De Leo Antonio , Gruppioni Elisa , Tarantino Giuseppe , Angelini Sabrina , Pession Andrea , Pantaleo Maria Abbondanza , Nannini Margherita 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00851

DOI=10.3389/fimmu.2020.00851

ISSN=1664-3224

ABSTRACT=PDGFRA mutations occur in in only about 5–7 % of gastrointestinal stromal tumors (GIST), notably with alterations on exon 12/14/18. The most frequent PDGFRA mutation is the exon 18 D842V, which is correlated to specific clinical-pathological features as the primary imatinib resistance and the higher indolence. 
Here, we present a gene expression profile (GEP) comparison of D842V versus PDGFRA mutant other than D842V (non-D842V). GEP was followed by in silico bioinformatic analysis aimed to evaluate differential expression, tumor microenvironment composition and pathway enrichment.
We found a large set of oncogenes, transcription factors and nuclear receptors downregulated in D842V mutant. Conversely, D842V showed 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 D842V mutant subgroup, that is predictive of immunotherapy response.
PDGFRA D842V versus non-D842V GIST display a different expression profile, with a prominent immunological signature, that could represent a proof of principle for testing immunotherapeutic strategies in this drug-orphan subset of GIST.