Hao Cheng1, Tian Qiu1, Su-Sheng Shi1. 1. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China.
Abstract
BACKGROUND: In gastrointestinal stromal tumor (GIST), mutually exclusive gain-of-function mutations of c-kit and PDGFRα are associated with different mutation-dependent clinical features. We analyzed clinico-pathologic features and genotypes of GIST among patients in China. METHODS: Adult patients with GIST in the stomach, small intestine, colorectum, or extra-gastrointestinal areas were enrolled in this study. These patients had been subjected to surgical resection without imatinib (Gleevec) treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2009 to January 2019. Samples were obtained for histopathologic examination. Mutations in c-kit and PDGFRα genes were analyzed by PCR and next generation sequencing (NGS). Clinico-pathologic characteristics of each gene were also analyzed. RESULTS: A total of 58 GIST patients was enrolled in this study. In terms of genotypes, there were 51 (87.9%) c-kit mutations, 5 (8.6%) PDGFRα mutations, and 2 (3.4%) wild-type mutations. In terms of cell types, there were 40 cases (69.0%) with spindle cell type, 3 cases (5.2%) with epithelioid cell type and 3 cases (5.2%) with mixed spindle-epithelioid cell type. Among the 4 mutant forms of c-kit exon-11, the most common were point mutations in 16 cases (38.1%), deletion mutations in 13 cases (31.0%), insertion mutations in 4 cases (9.5%), and mixed mutations in 9 cases (21.4%). Based on risk grade classification of the National Institutes of Health (NIH), 3 cases (5.2%) were very-low risk, 9 cases (15.5%) were low risk, 19 cases (32.8%) were medium risk, and 23 cases (39.7%) were high risk. Significant differences in cell type were identified across different gene types (P = 0.022). Similarly, differences in tumor risk were found among different mutant forms of c-kit gene exon-11 (P = 0.039). CONCLUSION: With c-kit mutations, spindle cell type prevalence exceeded that of the epithelioid cell type and mixed spindle-epithelioid cell type. Spindle and mixed spindle-epithelioid cell types were the most prevalent in the category of PDGFRα mutations. In wild type cases, spindle and epithelioid cell types were the most common. A high risk of deletion and mixed mutations, and intermediate risk of point and insertion mutations were observed in c-kit exon-11 mutation type. IJCEP
BACKGROUND: In gastrointestinal stromal tumor (GIST), mutually exclusive gain-of-function mutations of c-kit and PDGFRα are associated with different mutation-dependent clinical features. We analyzed clinico-pathologic features and genotypes of GIST among patients in China. METHODS: Adult patients with GIST in the stomach, small intestine, colorectum, or extra-gastrointestinal areas were enrolled in this study. These patients had been subjected to surgical resection without imatinib (Gleevec) treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2009 to January 2019. Samples were obtained for histopathologic examination. Mutations in c-kit and PDGFRα genes were analyzed by PCR and next generation sequencing (NGS). Clinico-pathologic characteristics of each gene were also analyzed. RESULTS: A total of 58 GIST patients was enrolled in this study. In terms of genotypes, there were 51 (87.9%) c-kit mutations, 5 (8.6%) PDGFRα mutations, and 2 (3.4%) wild-type mutations. In terms of cell types, there were 40 cases (69.0%) with spindle cell type, 3 cases (5.2%) with epithelioid cell type and 3 cases (5.2%) with mixed spindle-epithelioid cell type. Among the 4 mutant forms of c-kit exon-11, the most common were point mutations in 16 cases (38.1%), deletion mutations in 13 cases (31.0%), insertion mutations in 4 cases (9.5%), and mixed mutations in 9 cases (21.4%). Based on risk grade classification of the National Institutes of Health (NIH), 3 cases (5.2%) were very-low risk, 9 cases (15.5%) were low risk, 19 cases (32.8%) were medium risk, and 23 cases (39.7%) were high risk. Significant differences in cell type were identified across different gene types (P = 0.022). Similarly, differences in tumor risk were found among different mutant forms of c-kit gene exon-11 (P = 0.039). CONCLUSION: With c-kit mutations, spindle cell type prevalence exceeded that of the epithelioid cell type and mixed spindle-epithelioid cell type. Spindle and mixed spindle-epithelioid cell types were the most prevalent in the category of PDGFRα mutations. In wild type cases, spindle and epithelioid cell types were the most common. A high risk of deletion and mixed mutations, and intermediate risk of point and insertion mutations were observed in c-kit exon-11 mutation type. IJCEP
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