BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC...BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC.We recommend using these novel markers to assist in clinical decision-making.展开更多
●AIM:To describe the complex,overlapping phenotype of four Chinese patients with inherited retinal dystrophies(IRDs)who harbored two pathogenic genes simultaneously.●METHODS:This retrospective study included 4 patie...●AIM:To describe the complex,overlapping phenotype of four Chinese patients with inherited retinal dystrophies(IRDs)who harbored two pathogenic genes simultaneously.●METHODS:This retrospective study included 4 patients affected with IRDs.Medical and ophthalmic histories were obtained,and clinical examinations were performed.A specific Hereditary Eye Disease Enrichment Panel(HEDEP)based on exome capture technology was used for genetic screening.●RESULTS:Four patients were identified to harbor disease-causing variants in two different genes.Patient retinitis pigmentosa(RP)01-II:1 exhibited both classical ABCA4-induced Stargardt disease(STGD)1 and USH2 Aassociated RP,patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP,patient RP03-II:1 exhibited both USH2 A-induced autosomal recessive retinitis pigmentosa(arRP)syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa(adRP),and patient RP04-II:2 exhibited USH2 Ainduced arRP syndrome and EYS-induced arRP at the same time.●CONCLUSION:Our study demonstrates that genotype–phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease.展开更多
Gastrointestinal(GI)cancer has a high tumor incidence and mortality rate worldwide.Despite significant improvements in radiotherapy,chemotherapy,and targeted therapy for GI cancer over the last decade,GI cancer is cha...Gastrointestinal(GI)cancer has a high tumor incidence and mortality rate worldwide.Despite significant improvements in radiotherapy,chemotherapy,and targeted therapy for GI cancer over the last decade,GI cancer is characterized by high recurrence rates and a dismal prognosis.There is an urgent need for new diagnostic and therapeutic approaches.Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer.Here we review the application and status of precision medicine in GI cancer.Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy.With the introduction of gene panels including next-generation sequencing,it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer.Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors,novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs.These progressions will make it feasible to incorporate clinical,genome-based,and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.展开更多
下一代测序(next generation sequencing,NGS)技术已经在临床实验室中得到应用。该技术的发展以及检测规模和应用范围的扩大,使基因检测成本大大降低。NGS技术在临床上的应用在不断地扩大,如疾病靶向基因组套检测、个体外显子组或全基...下一代测序(next generation sequencing,NGS)技术已经在临床实验室中得到应用。该技术的发展以及检测规模和应用范围的扩大,使基因检测成本大大降低。NGS技术在临床上的应用在不断地扩大,如疾病靶向基因组套检测、个体外显子组或全基因组分析等。同时,NGS技术也进一步改善了治疗决策和对某疾病高危人群的预测。然而,NGS技术的发展也充满了挑战性,包括测序平台和技术更新带来的选择困惑、测序结果的临床验证的不一致性问题等。为了帮助临床实验室更好地了解NGS技术、解决临床验证和正确选择NGS测序平台和方法,以及持续监控NGS并保证高质量的测序结果及其临床解释,本文结合美国医学遗传学和基因组学会(American College of Medical Genetics and Genomics,ACMG)关于NGS技术在临床上的应用的专业标准和指南进行归纳和讨论,供我国分子诊断工作者制定国内行业标准时参考。展开更多
基金Supported by the Ministry of Science and Technology,Taiwan,No.MOST 104-2314-B-016-010-MY2 and No.MOST 106-2320-B-016-018the Ministry of National Defense,Taiwan,No.MAB-107-075,No.MAB-108-057and No.MAB-109-061
文摘BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC.We recommend using these novel markers to assist in clinical decision-making.
基金Supported by the National Natural Science Foundation of China(No.81770966,No.81470666,No.81271046)a Joint Program of Beijing Municipal NaturalScience Foundation(Category B)Beijing Educational committee(No.KZ201510025025).
文摘●AIM:To describe the complex,overlapping phenotype of four Chinese patients with inherited retinal dystrophies(IRDs)who harbored two pathogenic genes simultaneously.●METHODS:This retrospective study included 4 patients affected with IRDs.Medical and ophthalmic histories were obtained,and clinical examinations were performed.A specific Hereditary Eye Disease Enrichment Panel(HEDEP)based on exome capture technology was used for genetic screening.●RESULTS:Four patients were identified to harbor disease-causing variants in two different genes.Patient retinitis pigmentosa(RP)01-II:1 exhibited both classical ABCA4-induced Stargardt disease(STGD)1 and USH2 Aassociated RP,patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP,patient RP03-II:1 exhibited both USH2 A-induced autosomal recessive retinitis pigmentosa(arRP)syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa(adRP),and patient RP04-II:2 exhibited USH2 Ainduced arRP syndrome and EYS-induced arRP at the same time.●CONCLUSION:Our study demonstrates that genotype–phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease.
基金Supported by KAKENHI(Grant-in-Aid for Scientific Research),No.18H02883
文摘Gastrointestinal(GI)cancer has a high tumor incidence and mortality rate worldwide.Despite significant improvements in radiotherapy,chemotherapy,and targeted therapy for GI cancer over the last decade,GI cancer is characterized by high recurrence rates and a dismal prognosis.There is an urgent need for new diagnostic and therapeutic approaches.Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer.Here we review the application and status of precision medicine in GI cancer.Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy.With the introduction of gene panels including next-generation sequencing,it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer.Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors,novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs.These progressions will make it feasible to incorporate clinical,genome-based,and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.
文摘下一代测序(next generation sequencing,NGS)技术已经在临床实验室中得到应用。该技术的发展以及检测规模和应用范围的扩大,使基因检测成本大大降低。NGS技术在临床上的应用在不断地扩大,如疾病靶向基因组套检测、个体外显子组或全基因组分析等。同时,NGS技术也进一步改善了治疗决策和对某疾病高危人群的预测。然而,NGS技术的发展也充满了挑战性,包括测序平台和技术更新带来的选择困惑、测序结果的临床验证的不一致性问题等。为了帮助临床实验室更好地了解NGS技术、解决临床验证和正确选择NGS测序平台和方法,以及持续监控NGS并保证高质量的测序结果及其临床解释,本文结合美国医学遗传学和基因组学会(American College of Medical Genetics and Genomics,ACMG)关于NGS技术在临床上的应用的专业标准和指南进行归纳和讨论,供我国分子诊断工作者制定国内行业标准时参考。
