Stella Morrison

mutations to help predict the progression of gastrointestinal stromal tumors (GISTs), according to a new meta-analysis published in

mutations are not associated with higher risk of mortality, several studies have demonstrated that the mutations, especially those involving exon 9, can predict GIST progression. The predictions can help physicians decide whether or not to use tyrosine kinase inhibitors (TKIs), such as imatinib, to treat specific GI tumors.

mutation status is another evaluable factor to estimate prognosis in GISTs, in addition to tumor size and mitotic counts," said lead author Lin Yan, MD, department of oncology, Shandong Jiaotong Hospital, Jinan, China, et al in the study.

The analysis found patients with GIST exhibiting exon 9 mutations did not respond as well to TKIs as patients with other

"Previous studies indicated the response to imatinib treatment was worse in patients whose tumors harbored

exon 11 mutations," said Yan et al in the study. "Therefore, it is essential to identify mutation status to predict its response to TKIs and prognosis."

mutations most frequently occur in KIT exon 11, followed by KIT exon 9. Less frequently, mutations occur in the ATP-binding pocked (exon 13) or activation loop (exon 17). Although many types of

mutations have been observed in GISTs throughout previous studies, a meta-analysis published in

notes that, "controversy still exists concerning their prognostic and predictive value."

For the meta-analysis conducted by Lin Yan et al, researchers reviewed 18 prior studies culled from PubMed, EMBASE, and Web of Science, which had evaluated how various

To qualify, the studies had to address the relationship between

mutation and clinicopathological significance of GISTs, as well as the analysis of the prognosis in patients with GISTs. Studies with overlapping databases, insufficient data or methodological inconsistencies were excluded from the analysis. All 18 studies were deemed "of a relatively high quality" according to the Newcastle Ottawa Quality Assessment Scale.

The meta-analysis found that whether the tumor presented in the stomach or the small intestine, the progression-free survival (PFS) of patients with GIST was significantly worse when the patient's tumors exhibited exon 9 mutations. The 5-year PFS rate was significantly lower in patients with KIT exon 11 deletion, particularly when weighed against other exon 11 mutations. The 5-year PFS rate was significantly worse in patients whose KIT exon 11 deletions involved codon 557-558. Size of the tumor mattered as well:

mutations were observed more frequently in large GISTs (&ge;5 cm) than in smaller GISTs (&le;5 cm).

exon 9 mutation responded worse to imatinib treatment than those who harbored

exon 11 mutations, indicating that GISTs that exhibited the KIT exon 9 mutation could be used as an indicator in the progression of GISTs.

mutational status has prognostic significance for patients with GISTs," said Yan et al, in the study. "GIST patients with

exon 9 mutations have higher risk of progression than those with exon 11 mutations. Deletion of KIT exon 11, particularly codon 557-558 deletion of KIT exon 11, was a valuable predictor of prognosis for patients with GISTs."

Yan, L. et al.&nbsp;Clinicopathological significance of&nbsp;c-KIT&nbsp;mutation in gastrointestinal stromal tumors: a systematic review and meta-analysis.&nbsp;

. 5, 13718; doi: 10.1038/srep13718 (2015).

Wozniak, A. et al.&nbsp;Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience.

23, 353360, 10.1093/annonc/mdr127 mdr127 (2012).

Lasota, J. &&nbsp;Miettinen, M.&nbsp;Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours.&nbsp;

53, 245266, 10.1111/j.1365-2559.2008.02977.x HIS2977 (2008).

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Physicians may be able to use KIT mutations to help predict the progression of gastrointestinal stromal tumors (GISTs), according to a new meta-analysis published in Nature Scientific Reports.

Stella Morrison | Authors

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