Prognosis and predictive value of KIT exon 11 deletion in GISTs

Abstract

BACKGROUND: KIT exon 11 mutations are observed in 60% of gastrointestinal stromal tumours (GIST). Exon 11 codes for residues Tyr568 and Tyr570, which play a major role in signal transduction and degradation of KIT. Our aim was to compare the outcome of patients with deletion of both Tyr568 -570 (delTyr) and the most frequent deletion delWK557 -558 (delWK). METHODS: Pathology and clinical characteristics of 68 patients with delTyr (n ¼ 26) or delWK (n ¼ 42) were reviewed and compared. RESULTS: GISTs with delTyr were more frequently extragastric than those with delWK (69 vs 26%, Po0.0005). After curative surgery, median relapse-free survival were 10.8 and 11.1 months for patients with delTyr (n ¼ 14) and delWK (n ¼ 29), respectively (P ¼ 0.92). All patients treated with imatinib for a non-resectable or metastatic GIST had an objective response (n ¼ 15) or a stable disease (n ¼ 21) as best response, regardless of mutation. Median progression-free survival with imatinib were 21.9 and 18.9 months for patients with GIST with delTyr (n ¼ 14) and delWK (n ¼ 22), respectively (P ¼ 0.43). CONCLUSION: In this large retrospective series, the type of KIT exon 11 mutation was correlated with the origin of GIST, but not with prognosis or response to imatinib.

Molecular characterization of an Italian series of sporadic GISTs

“…In our case series most of the KIT mutations identified were located at exon 11, between codon 551 and codon 580, where most of the known mutations have been reported so far [12]. This position has been suggested to be associated with malignant tumor behavior [13,14]. However, we were unable to establish a genotype-phenotype correlation to confirm this hypothesis.…”

“…However, we were unable to establish a genotype-phenotype correlation to confirm this hypothesis. The duplications we identified also lie in the regions previously described [13].…”

Hemoperitôneo secundário a GIST gástrico c-KIT negativo e anticorpo anti-DOG1 positivo

“…As described in the literature, the first acute symptom of this patient was gastrointestinal hemorrhage. Bleeding is present in approximately 40% of cases (6,7) . DOG1 is a membrane protein discovered through analysis of the gene expression patterns of GIST, which showed to be a useful immunohistochemical marker (8) .…”

Les tumeurs stromales gastro-intestinales (GIST)

“…Les techniques d'analyse utilisées ensuite varient suivant les laboratoires et le type de mutation recherchée. De nombreux auteurs se sont intéressés à la valeur pronostique des mutations de KIT et PDGFRA dans les GIST [18,[20][21][22][23], et les résultats sont parfois contradictoires. Ceci s'explique par le caractère rétrospectif de la quasi totalité des études, la petite taille des effectifs (tumeurs rares), l'hétérogénéité des méthodes de détection des mutations et le biais de sélection des patients.…”