Deoxyribonucleic acid(DNA)genetic markers and ribonucleic acid(RNA)molecular markers have been widely used in forensic practices including individual identification,parentage testing,body fluid identification,determin...Deoxyribonucleic acid(DNA)genetic markers and ribonucleic acid(RNA)molecular markers have been widely used in forensic practices including individual identification,parentage testing,body fluid identification,determination of the age of stains,and molecular pathological diagnosis.Variant information of biological evidence and their interrelation could be revealed by the integrated detection of DNA/RNA markers.The integrated detection workflow aims to simplify working procedures,reduce time consuming and save valuable samples collected from crime scenes.Next-generation sequencing(NGS)may be an effective method for integrated DNA/RNA detection.In this review,DNA/RNA co-extraction strategies,simultaneous detection methods based on capillary electrophoresis were summarized.Research on NGS-based integrated detection methods of DNA and RNA markers was reviewed to provide a reference for forensic medicine researches and applications.展开更多
Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been report...Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been reported.Methods:We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identifybiomarkers for a response to bevacizumab-containing treatment.The molecular analysis comprised whole-exomesequencing,ribonucleic acid sequencing,and a methylation array on patient tissues.Results:Genomic and molecularcharacterization was successfully conducted in 103 patients.Six of 103 CRC samples were hypermutated,and none ofthe non-hypermutant tumors were microsatellite unstable.Among those 103 patients,89 had adenocarcinoma(ADC),15 were diagnosed with mucinous ADC,and six had signet-ring cell carcinoma(SRCC).Consensus molecular subtype(CMS)2 was unique to ADC.Of the four SRCCs,two were CMS1,one was CMS4,and the other was CMS3.APCmutation status was a significantly enriched factor in responders to bevacizumab treatment.Fibroblast growth factorreceptor(FGFR)1/2 signaling was upregulated in non-responders,whereas cell cycle,transfer ribonucleic acidprocessing,nucleotide excision repair,and oxidative phosphorylation pathways were enriched in responders.Inaddition,IGF1 was differentially expressed in non-responders(log2 fold change=−1.43,p=4.11×10^(−5),falsediscovery rate=0.098),and FLT1 was highly methylated in non-responders(p=7.55×10^(−3)).When the molecularpathways were reanalyzed separately according to the backbone chemotherapy(FOLFOX vs.FOLFIRI),thesignificance of the molecular pathways varied according to the backbone chemotherapy.Conclusions:This studysought a subset of CRC patients with a distinct clinical response to chemotherapy containing bevacizumab.Ourresults need to be validated in a large group of homogenous patient cohort and examined according to the differentchemotherapy backbones to create personalized therapeutic opportunities in CRC.展开更多
基金supported by the Ministry of Public Security of China(2019GABJC15)the Institute of Forensic Science,Ministry of Public Security of China(2018JB007).
文摘Deoxyribonucleic acid(DNA)genetic markers and ribonucleic acid(RNA)molecular markers have been widely used in forensic practices including individual identification,parentage testing,body fluid identification,determination of the age of stains,and molecular pathological diagnosis.Variant information of biological evidence and their interrelation could be revealed by the integrated detection of DNA/RNA markers.The integrated detection workflow aims to simplify working procedures,reduce time consuming and save valuable samples collected from crime scenes.Next-generation sequencing(NGS)may be an effective method for integrated DNA/RNA detection.In this review,DNA/RNA co-extraction strategies,simultaneous detection methods based on capillary electrophoresis were summarized.Research on NGS-based integrated detection methods of DNA and RNA markers was reviewed to provide a reference for forensic medicine researches and applications.
基金supported by a grant of the Korean Health Technology R&D Project through the Korean Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(Grant Number:HR20C0025).
文摘Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been reported.Methods:We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identifybiomarkers for a response to bevacizumab-containing treatment.The molecular analysis comprised whole-exomesequencing,ribonucleic acid sequencing,and a methylation array on patient tissues.Results:Genomic and molecularcharacterization was successfully conducted in 103 patients.Six of 103 CRC samples were hypermutated,and none ofthe non-hypermutant tumors were microsatellite unstable.Among those 103 patients,89 had adenocarcinoma(ADC),15 were diagnosed with mucinous ADC,and six had signet-ring cell carcinoma(SRCC).Consensus molecular subtype(CMS)2 was unique to ADC.Of the four SRCCs,two were CMS1,one was CMS4,and the other was CMS3.APCmutation status was a significantly enriched factor in responders to bevacizumab treatment.Fibroblast growth factorreceptor(FGFR)1/2 signaling was upregulated in non-responders,whereas cell cycle,transfer ribonucleic acidprocessing,nucleotide excision repair,and oxidative phosphorylation pathways were enriched in responders.Inaddition,IGF1 was differentially expressed in non-responders(log2 fold change=−1.43,p=4.11×10^(−5),falsediscovery rate=0.098),and FLT1 was highly methylated in non-responders(p=7.55×10^(−3)).When the molecularpathways were reanalyzed separately according to the backbone chemotherapy(FOLFOX vs.FOLFIRI),thesignificance of the molecular pathways varied according to the backbone chemotherapy.Conclusions:This studysought a subset of CRC patients with a distinct clinical response to chemotherapy containing bevacizumab.Ourresults need to be validated in a large group of homogenous patient cohort and examined according to the differentchemotherapy backbones to create personalized therapeutic opportunities in CRC.
