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

Rapisuwon, Sutheea,b; Parks, Kelliea,b; Al-Refaie, Waddaha,c; Atkins, Michael B.a,b

doi: 10.1097/CMR.0000000000000102
Short Communications

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.

aDivision of Hematology/Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center

bMelanoma Disease Group, Medstar-Georgetown Cancer Network, Washington, District of Columbia

cDivision of Surgical Oncology, Medstar-Georgetown University Hospital, USA

Correspondence to Michael B. Atkins, MD, Georgetown-Lombardi Comprehensive Cancer Center, New Research Building, Suite 501E, 3970 Reservoir Rd, Washington, DC 20057, USA Tel: +1 202 687 2795; fax: +1 202 687 1370; e-mail:

Received April 14, 2014

Accepted May 19, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins