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KIT Gene Mutations In Malignant Melanoma - Background Information

Activating mutations of the KIT tyrosine kinase are present in a number of human malignancies, including GI stromal tumors, mast cell disease, AML, seminoma and (rarely) melanoma. This test is designed primarily to detect mutations that are commonly found in GI stromal tumors and have been proven in clinical trials to correlate with the likelihood of response to treatment with imatinib mesylate (Gleevec™).1-5 The rare mutations reported in melanoma have been in exons 11, 13 and 17.6-7 These mutations are of the type that may be sensitive to imatinib.

References

  1. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol 22:3813-3825, 2004.
  2. Debiec-Rychter M, Raf Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay J-Y, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, Judson I. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 42:1093-103, 2006
  3. Heinrich MC, Shoemaker JS, Corless CL, Hollis D, Demetri GD, Bertagnolli MM, Fletcher JA. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings. Vol 23, No. 16S, Part I of II (June 1 Supplement), 2005: Abstract 7.
  4. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen C-J, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CDM, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib mesylate response in patients with metastatic gastrointestinal stromal tumor. J Clin Onc 21:4342-4349, 2003.
  5. Debiec-Rychter M, Dumez H, Judson I, Wasag B, Verweij J, Brown M, Dimitrijevic S, Sciot R, Stul M, Vranck H, Scurr M, Hagemeijer A, Van Glabbeke M, Van Oosterom AT. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 40:689-95, 2004.
  6. Willmore-Payne C, Holden JA, Hirschowitz S, Layfield LJ. BRAF and c-kit gene copy number in mutation-positive malignant melanoma. Hum Pathol. 37:520-7, 2006.
  7. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006 Sep 10;24(26):4340-6.

Links: Pathology Translational Research, Research Tests Available, GIST, Mastocytosis/MPD/AML, Melanoma