Comprehensive molecular screening by next generation sequencing reveals a distinctive mutational profile of / genes and novel genomic alterations: results from a 20-year cohort of patients with GIST from north-western Greece.

Introduction: Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms that usually carry an activating mutation in or platelet-derived growth factor receptor alpha () genes with predictive and prognostic significance. We investigated the extended mutational status of GIST in a patient population of north-western Greece in order to look at geopraphic/genotypic distinctive traits.

Patient And Methods: Clinicopathological and molecular data of 38 patients diagnosed from 1996 to 2016 with GIST in the region of Epirus in Greece were retrospectively assessed. Formalin-fixed paraffin-embedded tumours were successfully analysed for mutations in 54 genes with oncogenic potential. Next generation sequencing was conducted by using the Ion AmpliSeqCancer Hotspot Panel V.2 for DNA analysis (Thermofisher Scientific).

Results: Among 38 tumours, 24 (63.16%) and seven (18.42%) of the tumours harboured mutations in the and genes, respectively, while seven (18.42%) tumours were negative for either or mutation. No mutations were detected in five (13.16%) cases. Concomitant mutations of and fibroblast growth factor receptor 3 () genes were observed in two patients with gene mutation. Two patients with / wild-type GIST had mutations in either or phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha () genes. There was no significant survival difference regarding the exonic site of mutation in either or gene. The presence of a mutation in pathway effectors downstream of or , such as , or , was associated with poor prognosis. Adverse prognosticators were also high mitotic index and the advanced disease status at diagnosis.

Conclusions: We report comparable incidence of and mutation in patients with GIST from north-western Greece as compared with cohorts from other regions. Interestingly, we identified rare mutations on , and genes in patients with poor prognosis.