Reference Detail

Ref Type

Journal Article

PMID

(25003536)

Authors

Rapisuwon S, Parks K, Al-Refaie W, Atkins MB

Title

Novel somatic KIT exon 8 mutation with dramatic response to imatinib in a patient with mucosal melanoma: a case report.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Melanoma research	24	5	2014 Oct	509-11	Melanoma Res

URL

Abstract Text

Primary mucosal melanomas represent ∼1.3% of all cases of melanoma diagnosed in the USA. The sinonasal location is the most common primary site. Mutations in the KIT gene occur in 10-22% of mucosal melanomas. Tumor response to imatinib mesylate has been reported in about half of the patients with tumors harboring KIT mutations. Responses are almost exclusively restricted to tumors with mutations in KIT exon 9 or 11. We report a case of a patient with a sinonasal mucosal melanoma with a novel exon 8 mutation (C443S) who had marked initial response to imatinib. Somatic exon 8 KIT mutations have not been previously reported in mucosal melanoma or in other human solid tumors; however, such mutations have been reported in canine and feline mast cell tumors. Protein transcripts from exon 8 play an important role in the structural and functional integrity of the extracellular domain of KIT. In preclinical studies, a mutation in exon 8 led to autophosphorylation, independent of KIT ligand, and constitutive activation of the tyrosine kinase. This biology may explain the successful application of imatinib in animals with tumors harboring exon 8 KIT mutations and in our patient with mucosal melanoma. This report expands the population of patients with melanoma who might benefit from imatinib to those with somatic exon 8 KIT mutations. Such mutations should be looked for in patients with mucosal melanoma.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
KIT	C443S	missense	unknown	KIT C443S lies within Ig-like C2-type domain 5 of the Kit protein (UniProt.org). C443S has been identified in the scientific literature (PMID: 25003536), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2023).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
KIT C443S	mucosal melanoma	sensitive	Imatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with mucosal melanoma harboring KIT C443S demonstrated a substantial response to Gleevec (imatinib) in the first two weeks and then developed progression at 15 weeks (PMID: 25003536).	25003536