Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Gianni Pantuso, Daniele Fanale, Viviana Bazan, Alessandro Perez, Alessia Fiorino, Erika Pedone, Daniela Cabibi, Chiara Brando, Giuseppe Badalamenti, Lorena Incorvaia, Giuseppa Graceffa, Antonio Galvano, Nadia Barraco, Antonio Russo, Antonio Galvano, Marta Castiglia, Alessia Pivetti, Nadia Barraco, Alessandro Perez, Daniele FanaleMarco Bono, Alessia Fiorino, Daniela Cancelliere, Chiara Brando, Giuseppe Badalamenti, Annalisa Bonasera, Laura Algeri, Erika Pedone, Ida De Luca, Massimiliano Cani, Lidia Rita Corsini, Antonio Russo, Giuseppa Graceffa, Gianni Pantuso, Bruno Vincenzi, Alessia Pivetti, Annalisa Bonasera, Antonino Russo, Daniela Cancelliere, Laura Algeri

Risultato della ricerca: Articlepeer review

1 Citazioni (Scopus)


Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase (KIT) exon 11 PV were included in the study. We analyzed the type and codon location of the PV according to clinicopathological characteristics and clinical outcome; the metastatic sites in relapsed patients were also investigated. Results: Tumors harboring a KIT exon 11 deletion or deletion/insertion involving the 557 and/or 558 codons, showed a more aggressive clinical behavior compared with tumors carrying deletion/deletion/insertion in other codons, or tumors with duplication/insertion/single-nucleotide variant (SNV) (7-year RFS: 50% versus 73.1% versus 88.2%, respectively; p < 0.001). Notably, among 18 relapsed patients with 557 and/or 558 deletion or deletion/insertion, 14 patients (77.8%) harbored deletions simultaneously involving 557 and 558 codons, while only 4 patients (22.2%) harbored deletions involving only 1 of the 557/558 codons. Thus, when 557 or 558 deletions occurred separately, the tumor showed a prognostic behavior similar to the GIST carrying deletions outside the 557/558 position. Remarkably, patients with GISTs stratified as intermediate risk, but carrying the 557/558 deletion, showed a similar outcome to the high-risk patients with tumors harboring deletions in codons other than 557/558, or duplication/insertion/SNV. Conclusion: Our data support the inclusion of the PV type and codon location in routine risk prediction models, and suggest that intermediate-risk patients whose GISTs harbor 557/558 deletions may also need to be treated with adjuvant imatinib like the high-risk patients.
Lingua originaleEnglish
pagine (da-a)17588359211049779-
Numero di pagine13
RivistaTherapeutic Advances in Medical Oncology
Stato di pubblicazionePublished - 2021

All Science Journal Classification (ASJC) codes

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