p.(L576P) -KIT mutation in GIST: favourable prognosis and sensitive to imatinib?

p.(L576P) -KIT mutation in GIST: favourable prognosis and sensitive to imatinib?

Cancer Biol Ther. 2016 Mar 4;:0

Authors: Noujaim J, Gonzalez D, Thway K, Jones RL, Judson I

Abstract
Exon 11 KIT mutations are found in a majority of gastrointestinal stromal tumours (GIST) and are usually predictive of response to imatinib, a KIT, PDGFRA and ABL inhibitor. Exon 11 mutations with poor sensitivity to imatinib and poor outcome can be observed on rare occasions, including p.(L576P). In silico and in vitro studies suggested a decreased binding affinity for imatinib in p.(L576P) KIT mutations, thereby offering an explanation for their poor outcome and poor response to standard therapy. These observations were further corroborated with anecdotal case reports of refractoriness or non-durable response to imatinib therapy. However, we describe the favourable response to imatinib and outcome in five p.(L576P)-KIT mutant GIST patients treated at a tertiary sarcoma referral center. The sensitivity of p.(L576P)-KIT mutations to imatinib, and the prognostic impact of this mutation need to be further evaluated in a larger cohort. Based on our observations, p.(L576P) mutated GISTs should be treated with standard first line imatinib therapy.

PMID: 26942271 [PubMed - as supplied by publisher]

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