This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma(ESCC),which if diagnosed at advanced stages has<30%five-year survival rate.Compa...This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma(ESCC),which if diagnosed at advanced stages has<30%five-year survival rate.Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues,we identified 35,577 differentially methylated CpG sites(DMCs)and characterized their distribution patterns.展开更多
Radiotherapy remains the mainstay for treatment of various types of human cancer;however,the clinical efficacy is often limited by radioresistance,in which the underlying mechanism is largely unknown.Here,using esopha...Radiotherapy remains the mainstay for treatment of various types of human cancer;however,the clinical efficacy is often limited by radioresistance,in which the underlying mechanism is largely unknown.Here,using esophageal squamous cell carcinoma(ESCC)as a model,we demonstrate that guanine nucleotide exchange factor 2(VAV2),which is overexpressed in most human cancers,plays an important role in primary and secondary radioresistance.We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation.展开更多
Esophageal squamous-cell carcinoma （ESCC） is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies （GWAS） of germline ...Esophageal squamous-cell carcinoma （ESCC） is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies （GWAS） of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma （CCGD-ESCC） database, which contains the associations of 69,593 single nucleotide polymorphisms （SNPs） with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients （survival GWAS） and gene expression （expression quantitative trait loci,eQTL） in 94 ESCC patients. Moreover, this database also provides the associations between8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http：//db.cbi.pku.edu.cn/ccgd/ESCCdb.展开更多
基金Supported by National Natural Science Foundation of China(81988101 to D.L.and C.W.)National Science Fund for Distinguished Young Scholars(81725015 to C.W.)+2 种基金Chinese Academy Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-013 to D.L.,C.W.and W.T.,2019-I2M-2-001 to D.L and C.W.)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023027 to C.W.)the National Key R&D Program of China(2021YFC2502000 to Y.L.).
文摘This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma(ESCC),which if diagnosed at advanced stages has<30%five-year survival rate.Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues,we identified 35,577 differentially methylated CpG sites(DMCs)and characterized their distribution patterns.
基金This project was supported by National Science Fund for Distinguished Young Scholars(81725015 to C.W.)Medical and Health Technology Innovation Project of Chinese Academy of Medical Sciences(2016-I2M-3-019 to D.L.,2016-I2M-4-002 to C.W.,2019-I2M-2-001 to D.L.and C.W.,2016-I2M-1-001 and 2019-12M-1-003 to W.T.)+1 种基金Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023027 to C.W.)National Natural Science Foundation of China(81988101 to D.L and C.W.).
文摘Radiotherapy remains the mainstay for treatment of various types of human cancer;however,the clinical efficacy is often limited by radioresistance,in which the underlying mechanism is largely unknown.Here,using esophageal squamous cell carcinoma(ESCC)as a model,we demonstrate that guanine nucleotide exchange factor 2(VAV2),which is overexpressed in most human cancers,plays an important role in primary and secondary radioresistance.We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation.
基金supported by CAMS Innovation Fund for Medical Sciences (Grant No. 2016-I2M-4-002 awarded to CW)the National Key R&D Program (Grant No. 2016YFC1302701 to CW and Grant No. 2016YFC0901603 to GG)
文摘Esophageal squamous-cell carcinoma （ESCC） is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies （GWAS） of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma （CCGD-ESCC） database, which contains the associations of 69,593 single nucleotide polymorphisms （SNPs） with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients （survival GWAS） and gene expression （expression quantitative trait loci,eQTL） in 94 ESCC patients. Moreover, this database also provides the associations between8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http：//db.cbi.pku.edu.cn/ccgd/ESCCdb.
