Objective:Lynch syndrome(LS)increases the risk of various cancers,including colorectal cancer,endometrial cancer and gastric cancer(GC).The incidence of LS among microsatellite instability-high(MSI-H)GC and their asso...Objective:Lynch syndrome(LS)increases the risk of various cancers,including colorectal cancer,endometrial cancer and gastric cancer(GC).The incidence of LS among microsatellite instability-high(MSI-H)GC and their association in South Korea remains underexplored.This study investigates LS-associated pathogenic germline variants in MSI-H GC patients using whole-exome sequencing(WES)on normal tissues.Methods:This retrospective study included patients who underwent gastrectomy for GC at Soonchunhyang University Bucheon and Cheonan Hospitals from January 2011 to October 2023.Among 1,537 patients screened for MSI status,127(8.3%)were identified as MSI-H.WES was performed on normal tissues from 123 patients.Pathogenic/likely pathogenic(P/LP)variants in mismatch repair(MMR)genes were identified using in silico models and protein loss assessments in corresponding tumor tissues.Results:Of the 127 MSI-H GC cases,characteristics aligned with typical MSI-H GC.The average age was70.02 years,with 98(77.2%)located in the lower body and 81(63.8%)of the intestinal type.All five MSI markers were positive in 46.5%of cases,whereas four markers were positive in 27.6%.Of the MSI-H GCs,10 LS candidates were identified.Three patients had known P/LP variants[MLH1(c.1758dup),MSH6(c.3261dup),MSH2(c.1241T>C)].Seven patients had variants of unknown significance(VUS)in MMR genes.Six(4.9%)patients were identified as having LS or possible LS,including one patient with the MLH1(c.1153C>T)variant previously classified as VUS but now considered LS-associated.Conclusions:This large-scale screening for LS in MSI-H GC patients using retrospective samples confirmed the lower incidence of LS than those of colorectal or endometrial cancer and GC patients in Western countries,emphasizing the need for clinical consideration in managing MSI-H GC patients.展开更多
Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient clas...Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer patients.Methods:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals.The SPC test was employed to stratify patients into risk groups,and its feasibility and performance were evaluated.The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment.Furthermore,3-year disease-free survivals of risk groups were analyzed.Results:The SPC test met the primary endpoint criteria.The 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment started.In a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d.Furthermore,3-year disease-free survivals were significantly different between risk groups classified with SPC tests.Conclusions:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies.It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.展开更多
Gastric cancer(GC)is a pervasive global malignancy with high mortality rates due to distant metastasis[1].GC metastasis can occur via hematogenous route,peri-toneal route,and specifically through ovarian spread in fem...Gastric cancer(GC)is a pervasive global malignancy with high mortality rates due to distant metastasis[1].GC metastasis can occur via hematogenous route,peri-toneal route,and specifically through ovarian spread in females[2].Among these,peritoneal metastasis is the most prevalent and challenging condition to treat[3].The Cancer Genome Atlas(TCGA)has uncovered four molec-ular subtypes of GC:microsatellite instability,Epstein-Barr virus-related,chromosomal instability,and genomically stable[4].展开更多
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2022R1A2C2092005)the Soonchunhyang University Research Fund。
文摘Objective:Lynch syndrome(LS)increases the risk of various cancers,including colorectal cancer,endometrial cancer and gastric cancer(GC).The incidence of LS among microsatellite instability-high(MSI-H)GC and their association in South Korea remains underexplored.This study investigates LS-associated pathogenic germline variants in MSI-H GC patients using whole-exome sequencing(WES)on normal tissues.Methods:This retrospective study included patients who underwent gastrectomy for GC at Soonchunhyang University Bucheon and Cheonan Hospitals from January 2011 to October 2023.Among 1,537 patients screened for MSI status,127(8.3%)were identified as MSI-H.WES was performed on normal tissues from 123 patients.Pathogenic/likely pathogenic(P/LP)variants in mismatch repair(MMR)genes were identified using in silico models and protein loss assessments in corresponding tumor tissues.Results:Of the 127 MSI-H GC cases,characteristics aligned with typical MSI-H GC.The average age was70.02 years,with 98(77.2%)located in the lower body and 81(63.8%)of the intestinal type.All five MSI markers were positive in 46.5%of cases,whereas four markers were positive in 27.6%.Of the MSI-H GCs,10 LS candidates were identified.Three patients had known P/LP variants[MLH1(c.1758dup),MSH6(c.3261dup),MSH2(c.1241T>C)].Seven patients had variants of unknown significance(VUS)in MMR genes.Six(4.9%)patients were identified as having LS or possible LS,including one patient with the MLH1(c.1153C>T)variant previously classified as VUS but now considered LS-associated.Conclusions:This large-scale screening for LS in MSI-H GC patients using retrospective samples confirmed the lower incidence of LS than those of colorectal or endometrial cancer and GC patients in Western countries,emphasizing the need for clinical consideration in managing MSI-H GC patients.
基金partial financial support provided by Novomics (Seoul, Korea)
文摘Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer patients.Methods:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals.The SPC test was employed to stratify patients into risk groups,and its feasibility and performance were evaluated.The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment.Furthermore,3-year disease-free survivals of risk groups were analyzed.Results:The SPC test met the primary endpoint criteria.The 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment started.In a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d.Furthermore,3-year disease-free survivals were significantly different between risk groups classified with SPC tests.Conclusions:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies.It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.
基金supported by a National Research Foun-dation of Korea(NRF)grant funded by the Korean gov-ernment(MSIT)(2019R1C1C1006715,2022R1A2C2092005)by the Soonchunhyang University Research Fund.
文摘Gastric cancer(GC)is a pervasive global malignancy with high mortality rates due to distant metastasis[1].GC metastasis can occur via hematogenous route,peri-toneal route,and specifically through ovarian spread in females[2].Among these,peritoneal metastasis is the most prevalent and challenging condition to treat[3].The Cancer Genome Atlas(TCGA)has uncovered four molec-ular subtypes of GC:microsatellite instability,Epstein-Barr virus-related,chromosomal instability,and genomically stable[4].
