CDH1 germline mutations and hereditary diffuse gastric cancer in a Chinese population

【作者】 潘志文； 王明丽； 包叶江； 付志璇； 曹文明； 罗聪； 陈文虎； 徐笑红；

【机构】 浙江省肿瘤医院；

【摘要】 Background and Aims: Gastric cancer is among the most common high-morbidity and high-mortality cancers worldwide. Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer(HDGC) and have been identified across multiple ethnicities. However, CDH1 germline mutations have seldom been documented in Chinese HDGC patients, and their frequency in this population remains unclear. This study aimed to examine the frequency of CDH1 germline mutations in Chinese HDGC patients. Methods: In total, 167 patients meeting the 2015 testing criteria of HDGC for CDH1 germline mutations were recruited. Patient germline DNA was screened for CDH1 mutations by Sanger sequencing. Results: Eight missense and one nonsense CDH1 germline mutations were identified in 28 of 167 index cases(16.8%). Three CDH1 germline mutations c.76 G>A(Glu26 Lys),c.1990 A>C(Lys664 Gln), and c.2437 G>A(Glu813 Lys) were identified as new variants. The frequency of CDH1 mutations was 16.3% in hereditary diffuse gastric cancer(HDGC) and 17.3% in early onset diffuse gastric cancer(EODGC).In the early onset DGC cases, the CDH1 mutation rate in female patients was 21.3%, higher than that in male patients(10.7%). In contrast to previous reports that CDH1 mutations do not have hotspot characteristics, we found that up to 71.4% of CDH1 mutations in the 28 CDH1-mutant Chinese HDGC patients included 2607 G>A(E806 K).Conclusion: This is the first reported series of CDH1 mutation carriers among Chinese HDGC patients. These data reveal the type and frequency of CDH1 germline mutations in Chinese HDGC patients and indicate that CDH1 mutation screening should be recommended for HDGC patients, especially in early onset DGC cases.更多还原

【Abstract】 Background and Aims: Gastric cancer is among the most common high-morbidity and high-mortality cancers worldwide. Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer(HDGC) and have been identified across multiple ethnicities. However, CDH1 germline mutations have seldom been documented in Chinese HDGC patients, and their frequency in this population remains unclear. This study aimed to examine the frequency of CDH1 germline mutations in Chinese HDGC patients. Methods: In total, 167 patients meeting the 2015 testing criteria of HDGC for CDH1 germline mutations were recruited. Patient germline DNA was screened for CDH1 mutations by Sanger sequencing. Results: Eight missense and one nonsense CDH1 germline mutations were identified in 28 of 167 index cases(16.8%). Three CDH1 germline mutations c.76 G>A(Glu26 Lys),c.1990 A>C(Lys664 Gln), and c.2437 G>A(Glu813 Lys) were identified as new variants. The frequency of CDH1 mutations was 16.3% in hereditary diffuse gastric cancer(HDGC) and 17.3% in early onset diffuse gastric cancer(EODGC).In the early onset DGC cases, the CDH1 mutation rate in female patients was 21.3%, higher than that in male patients(10.7%). In contrast to previous reports that CDH1 mutations do not have hotspot characteristics, we found that up to 71.4% of CDH1 mutations in the 28 CDH1-mutant Chinese HDGC patients included 2607 G>A(E806 K).Conclusion: This is the first reported series of CDH1 mutation carriers among Chinese HDGC patients. These data reveal the type and frequency of CDH1 germline mutations in Chinese HDGC patients and indicate that CDH1 mutation screening should be recommended for HDGC patients, especially in early onset DGC cases.更多还原