Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan

Sinonasal Lymphoma is one of the constituents of lethal midline granuloma, which is a clinical term for progressive, destructive lesions affecting the midline of the face. The majority of sinonasal lymphomas, especially those showing polymorphous patterns of proliferation and thus termed polymorphic reticulosis, recently were categorized as sinonasal natural killer/T-cell lymphomas. They are more prevalent in Asia than Europe or North America and are associated with EBV infection. Twenty-three cases with sinonasal natur al killer/T-cell lymphomas were collected from two high-incidence regions: Beijing, China (14 cases) and Osaka, Japan (9 cases). c-kit mutations were analyzed on paraffin-embedded specimens by PCR-single-strand conformation p olymorphism followed by direct sequencing; the c-kit proto-oncogene encodes a receptor of tyrosine kinase, which plays an important role in the regula tion of normal and neoplastic hematopoiesis by the interaction with its spe cific ligand, termed stem cell factor. Twelve single nucleotide substitutio n mutations were seen in 23 cases. Ten of 14 Chinese cases (71.4%) had muta tions at exon 11 or exon 17, whereas only two of nine Japanese cases (22.2% ) had mutations, showing a significant difference in frequency between Chin ese and Japanese cases. Furthermore, seven of eight mutations (92%) in exon 17 occurred at codon 825 and three of four mutations (75%) in exon 11 occu rred at codon 561. Such a specificity has not been reported before, and the se results, taken together, suggest that location-specific differences in e tiological factors cause specific mutations in c-kit gene.