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

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Date
2016-05
ICR Author
Gonzalez de Castro, David
Judson, Ian
Jones, Robin
Thway, Khin
Author
Noujaim, J
Gonzalez, D
Thway, K
Jones, RL
Judson, I
Type
Journal Article
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Abstract
Exon 11 KIT mutations are found in a majority of gastrointestinal stromal tumors (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 favorable response to imatinib and outcome in 5 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.
URI
https://repository.icr.ac.uk/handle/internal/114
DOI
https://doi.org/10.1080/15384047.2016.1156263
Collections
  • Clinical Studies
Subject
Humans
Gastrointestinal Stromal Tumors
Prognosis
Mutation
Female
Male
Imatinib Mesylate
Research team
Sarcoma Clinical Trials (R Jones)
Language
eng
License start date
2016-05
Citation
Cancer biology & therapy, 2016, 17 (5), pp. 543 - 545

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