Type and gene location of kit mutations predict progression-free survival to first-line imatinib in gastrointestinal stromal tumors: A look into the exon

Viviana Bazan, Daniela Cabibi, Gianni Pantuso, Antonio Russo, Lorena Incorvaia, Tommaso Vincenzo Bartolotta, Giuseppe Badalamenti, Roberto Cannella, Daniele Fanale, Antonio Russo, Antonio Russo, Daniele Fanale, Ida De Luca, Giuseppe Badalamenti, Gianni Pantuso, Bruno Vincenzi

Risultato della ricerca: Articlepeer review

3 Citazioni (Scopus)

Abstract

In previous studies on localized GISTs, KIT exon 11 deletions and mutations involving codons 557/558 showed an adverse prognostic influence on recurrence-free survival. In the metastatic setting, there are limited data on how mutation type and codon location might contribute to progression-free survival (PFS) variability to first-line imatinib treatment. We analyzed the type and gene location of KIT and PDGFRA mutations for 206 patients from a GIST System database prospectively collected at an Italian reference center between January 2005 and September 2020. By describing the mutational landscape, we focused on clinicopathological characteristics according to the critical mutations and investigated the predictive role of type and gene location of the KIT exon 11 mutations in metastatic patients treated with first-line imatinib. Our data showed a predictive impact of KIT exon 11 pathogenic variant on PFS to imatinib treatment: patients with deletion or insertion/deletion (delins) in 557/558 codons had a shorter PFS (median PFS: 24 months) compared to the patients with a deletion in other codons, or duplication/insertion/SNV (median PFS: 43 and 49 months, respectively) (p < 0.001). These results reached an independent value in the multivariate model, which showed that the absence of exon 11 deletions or delins 557/558, the female gender, primitive tumor diameter (≤5 cm) and polymorphonuclear leucocytosis (>7.5 109/L) were significant prognostic factors for longer PFS. Analysis of the predictive role of PDGFRA PVs showed no significant results. Our results also confirm the aggressive biology of 557/558 deletions/delins in the metastatic setting and allow for prediction at the baseline which GIST patients would develop resistance to first-line imatinib treatment earlier.
Lingua originaleEnglish
pagine (da-a)1-15
Numero di pagine15
RivistaCancers
Volume13
Stato di pubblicazionePublished - 2021

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1300.1306???

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