Clinical characteristics of cutaneous and mucosal melanoma and c-KIT gene L576P mutation

Abstract

The impact of mutations in c-KIT gene for melanoma progress is now a proven fact. However, no clear-cut relationship between the presence of a mutation and melanoma course has been detected. We attempted detection of a correlation between L576P mutation in melanoma cells and its location and progress. The objects of the study were specimens ofprimary melanoma in sites, exposed to chronic UV irradiation as well as on mucosa membranes, on the palms and soles. Mutation L576P was detected in 3 (16%) of 19 patients with melanomas; all mutations were found on the melanomas located in the forearm. Mutation L576P was inessentialfor the characteristics of melanoma (tumor thickness according to Breslow, type of intratumorous lymphocytic infiltration, presence of pigment and ulcerations).

Keywords

c-KIT / CD 117 / melanoma / c-KIT / tyrosine kinase receptor / CD117

References

[1] Chen S.Q., Xiong A.Q. The progress and implication of stem cell factor. Basic Med. Sci. Clin. 2002; 22(5): 385-90.

[2] Liang J., Wu Y.L., Chen B.J., Zhang W., Tanaka Y., Sugiyama H. The c-Kit receptor-mediated signal transduction and tumorrelated diseases. Int. J. Biol. Sci. 2013; 9(5): 435-43.

[3] Yarden Y., Kuang W.J., Yang-Feng T., Coussens L., Munemitsu S., Dull T.J., et al. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987; 6(11): 3341-51.

[4] Lennartsson J., Rönnstrand L. Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev. 2012; 92(4); 1619-49.

[5] Sansal I., Sellers W.R. The biology and clinical relevance of the PTEN tumor suppressor pathway. J. Clin. Oncol. 2004; 22(14): 2954-63.

[6] Summy J.M., Gallick G.E. Treatment for Advanced Tumors: Src Reclaims Center Stage. Clin. Cancer Res. 2006; 12(5): 1398-401.

[7] Silva C.M. Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis. Oncogene. 2004; 23(48): 8017-23.

[8] Yasuda T., Kurosaki T. Regulation of lymphocyte fate by Ras/ERK signals. Cell Cycle. 2008; 7(23): 3634-40.

[9] Shen H.Q., Tang Y.M., Yang S.L., Qian B.Q., Song H., Shi S.W., Xu W.Q. Analysis of CD117 expression on leukemia cells. Zhonghua Xue Ye Xue Za Zhi. 2003; 24(5): 228-30.

[10] Tsao A.S., Kantarjian H., Thomas D., Giles F., Cortes J., Garcia-Manero G., et al. с-Kit receptor expression in acute leukemias-association with patient and disease characteristics and with outcome. Leuk. Res. 2004; 28(4): 373-8.

[11] Carvajal R.D., Antonescu C.R., Wolchok J.D., Chapman P.B., Roman R.A., Teitcher J., et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011; 305(22): 2327-34.

[12] Beadling C., Jacobson-Dunlop E., Hodi F.S., Le C., Warrick A., Patterson J., et al. KIT gene mutations and copy number in melanoma subtypes. Clin. Cancer Res. 2008; 14(21): 6821-8.

[13] Satzger I., Küttler U., Völker B., Schenck F., Kapp A., Gutzmer R. Anal mucosal melanoma with KIT-activating mutation and response to imatinib therapy-case report and review of the literature. Dermatology. 2010; 220(1): 77-81.

[14] Hodi F.S., Corless C.L., Giobbie-Hurder A., Fletcher J.A., Zhu M., Marino-Enriquez A., et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J. Clin. Oncol. 2013; 31(26): 3182-90.

[15] Torres-Cabala C.A., Wang W.L., Trent J., Yang D., Chen S., Galbincea J., et al. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod. Pathol. 2009; 22(11): 1446-56.

[16] Woodman S.E., Trent J.C., Stemke-Hale K., Lazar A.J., Pricl S., Pavan G.M., et al. Activity of dasatinib against L576P KIT mutant melanoma: Molecular, cellular, and clinical correlates. Mol. Cancer Ther. 2009: 8(8): 2079-85.

[17] Antonescu C.R., Busam K.J., Francone T.D., Wong G.C., Guo T., Agaram N.P., et al. L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition. Int. J. Cancer. 2007; 121(2): 257-64.

[18] Zhu Y.I., Fitzpatrick J.E. Expression of c-kit (CD117) in Spitz nevus and malignant melanoma. J. Cutan. Pathol. 2006; 33(1): 33-7.

[19] Dahl C., Abildgaard C., Riober-Hasen R., Steiniche T., Lade-Keller J., Guldberg P. KIT is a frequent target for epigenetic silencing in cutaneous melanoma. J. Invest. Dermatol. 2015; 135(2): 516-24.

[20] Aksenenko M.B., Kirichenko A.K., Ruksha T.G. Russian study of morphological prognostic factors characterization in BRAF-mutant cutaneous melanoma. Pathol. Res. Pract. 2015; 211(7): 521-7. doi: 10.1016/j.prp.2015.03.005.

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