Despite advancements in CAR-T therapy,over half of the lymphoma patients still face drug resistance or relapse.Seventy-nine Chinese patients with B-cell lymphoma provided 192 serum samples for circulating tumor DNA(ct...Despite advancements in CAR-T therapy,over half of the lymphoma patients still face drug resistance or relapse.Seventy-nine Chinese patients with B-cell lymphoma provided 192 serum samples for circulating tumor DNA(ct DNA)detection to identify the genomic features linked to prognosis during CAR-T cell therapy.Patients in complete remission and noncomplete remission groups were analyzed,and those with>10 ct DNA gene mutations before CAR-T cell therapy had significantly worse overall survival and progression-free survival rates than those with fewer mutations.MYD88,FAT1,and BTG2 mutations were correlated with poorer OS,whereas MUC16 mutations were correlated with better OS.Patients with TP53 mutation pretreatment had significantly lower CR rates than those without TP53 mutations(33.3%vs.68.1%,P=0.02).However,TP53 mutation pretreatment did not affect long-term patient survival.All patients with TP53 mutations 4 weeks after CAR-T cell therapy failed to achieve CR,with poorer OS(1-year OS rate:37.5%vs.66.4%;2-year OS rate:12.5%vs.56.3%,P=0.0023).Among patients with CR,those with BCR mutations at 4 weeks post-treatment exhibited poorer OS(2-year OS rate:40.9%vs.76.1%,P=0.035).One week after CAR-T cell therapy,patients without CDKN2A,CBLB,APC,SPEN,KMT2D,CARD11,FOXO1,or PDGFRB mutations were more likely to achieve CR(76.6%vs.28.6%,P<0.001)and had better OS(1-year OS rate:81.5%vs.38.9%,2-year OS rate:62.2%vs.5%,P<0.001)and PFS(1-year PFS rate:67.2%vs.0%,P<0.001).This study evaluated the genomic features and screened a gene set to predict CAR-T cell therapy efficacy in B-cell lymphoma,aiding clinicians in accurately evaluating efficacy and treatment decision-making.展开更多
Brassicaceae represents an important plant family from both a scientific and economic perspective.However,genomic features related to the early diversification of this family have not been fully characterized,especial...Brassicaceae represents an important plant family from both a scientific and economic perspective.However,genomic features related to the early diversification of this family have not been fully characterized,especially upon the uplift of the Tibetan Plateau,which was followed by increasing aridity in the Asian interior,intensifying monsoons in Eastern Asia,and significantly fluctuating daily temperatures.Here,we reveal the genomic architecture that accompanied early Brassicaceae diversification by analyzing two high-quality chromosome-level genomes for Meniocus linifolius(Arabodae;clade D)and Tetracme quadricornis(Hesperodae;clade E),together with genomes representing all major Brassicaceae clades and the basal Aethionemeae.We reconstructed an ancestral core Brassicaceae karyotype(CBK)containing 9 pseudochromosomes with 65 conserved syntenic genomic blocks and identified 9702 conserved genes in Brassicaceae.We detected pervasive conflicting phylogenomic signals accompanied by widespread ancient hybridization events,which correlate well with the early divergence of core Brassicaceae.We identified a successive Brassicaceae-specific expansion of the class I TREHALOSE-6-PHOSPHATE SYNTHASE 1(TPS1)gene family,which encodes enzymes with essential regulatory roles in flowering time and embryo development.The TPS1s were mainly randomly amplified,followed by expression divergence.Our results provide fresh insights into historical genomic features coupled with Brassicaceae evolution and offer a potential model for broad-scale studies of adaptive radiation under an ever-changing environment.展开更多
<i>Bacillus thuringiensis</i> (Bt) parasporal crystal proteins were well known to be toxic to certain insects and cytocidal activity against various human cancer cells. Bt serovar <i>coreanensis</...<i>Bacillus thuringiensis</i> (Bt) parasporal crystal proteins were well known to be toxic to certain insects and cytocidal activity against various human cancer cells. Bt serovar <i>coreanensis</i> ST7, non-pathogenic to insects and non-hemolytic, has an important parasporin, PS4Aa1 (Cry45Aa1), with potential toxicity to human cancer cells. In this study, we reported the feature of complete genome sequence and the cluster of orthologous groups of proteins function classification of ST7. Meanwhile, the evolutionary of ST7 was also studied. The genome data of ST7 will strongly contribute to a better understanding of the genomic diversity and evolution, and enrich the Bt genome database.展开更多
The development of the term‘imaging genomics’.Despite significant advancements in human genomics,the phenotypic and clinical relevance of genomic features remains largely unknown.Imaging genomics,also known as radio...The development of the term‘imaging genomics’.Despite significant advancements in human genomics,the phenotypic and clinical relevance of genomic features remains largely unknown.Imaging genomics,also known as radiogenomics,was proposed to find the associations between clinical image data and human genetic data,facilitating a better understanding of the molecular characteristics of diseases.Originally,imaging data are acquired mainly by Magnetic Resonance Imaging(MRI)for brain disease detection.展开更多
Digestive tract cancers(DTCs)are cancers that occur in the gastrointestinal tract and related organs,including esoph-ageal,gastric,and colorectal cancer.Since these types of cancer share similar endoderm developmental...Digestive tract cancers(DTCs)are cancers that occur in the gastrointestinal tract and related organs,including esoph-ageal,gastric,and colorectal cancer.Since these types of cancer share similar endoderm developmental origins,the genomic and other molecular features can possess many similarities.Therefore,it is urgent to explore the com-monalities of molecular characteristics and signaling path-ways in the tumor microenvironment among these diseases.展开更多
基金supported by the National Natural Science Foundation of China(82130003,82270234)the Sanming Project of Medicine in Shenzhen(SZSM202111004)。
文摘Despite advancements in CAR-T therapy,over half of the lymphoma patients still face drug resistance or relapse.Seventy-nine Chinese patients with B-cell lymphoma provided 192 serum samples for circulating tumor DNA(ct DNA)detection to identify the genomic features linked to prognosis during CAR-T cell therapy.Patients in complete remission and noncomplete remission groups were analyzed,and those with>10 ct DNA gene mutations before CAR-T cell therapy had significantly worse overall survival and progression-free survival rates than those with fewer mutations.MYD88,FAT1,and BTG2 mutations were correlated with poorer OS,whereas MUC16 mutations were correlated with better OS.Patients with TP53 mutation pretreatment had significantly lower CR rates than those without TP53 mutations(33.3%vs.68.1%,P=0.02).However,TP53 mutation pretreatment did not affect long-term patient survival.All patients with TP53 mutations 4 weeks after CAR-T cell therapy failed to achieve CR,with poorer OS(1-year OS rate:37.5%vs.66.4%;2-year OS rate:12.5%vs.56.3%,P=0.0023).Among patients with CR,those with BCR mutations at 4 weeks post-treatment exhibited poorer OS(2-year OS rate:40.9%vs.76.1%,P=0.035).One week after CAR-T cell therapy,patients without CDKN2A,CBLB,APC,SPEN,KMT2D,CARD11,FOXO1,or PDGFRB mutations were more likely to achieve CR(76.6%vs.28.6%,P<0.001)and had better OS(1-year OS rate:81.5%vs.38.9%,2-year OS rate:62.2%vs.5%,P<0.001)and PFS(1-year PFS rate:67.2%vs.0%,P<0.001).This study evaluated the genomic features and screened a gene set to predict CAR-T cell therapy efficacy in B-cell lymphoma,aiding clinicians in accurately evaluating efficacy and treatment decision-making.
基金supported by the Priority Research Program of the Chinese Academy of Sciences(CAS)(Grant No.XDA0440000 and XDB31000000).
文摘Brassicaceae represents an important plant family from both a scientific and economic perspective.However,genomic features related to the early diversification of this family have not been fully characterized,especially upon the uplift of the Tibetan Plateau,which was followed by increasing aridity in the Asian interior,intensifying monsoons in Eastern Asia,and significantly fluctuating daily temperatures.Here,we reveal the genomic architecture that accompanied early Brassicaceae diversification by analyzing two high-quality chromosome-level genomes for Meniocus linifolius(Arabodae;clade D)and Tetracme quadricornis(Hesperodae;clade E),together with genomes representing all major Brassicaceae clades and the basal Aethionemeae.We reconstructed an ancestral core Brassicaceae karyotype(CBK)containing 9 pseudochromosomes with 65 conserved syntenic genomic blocks and identified 9702 conserved genes in Brassicaceae.We detected pervasive conflicting phylogenomic signals accompanied by widespread ancient hybridization events,which correlate well with the early divergence of core Brassicaceae.We identified a successive Brassicaceae-specific expansion of the class I TREHALOSE-6-PHOSPHATE SYNTHASE 1(TPS1)gene family,which encodes enzymes with essential regulatory roles in flowering time and embryo development.The TPS1s were mainly randomly amplified,followed by expression divergence.Our results provide fresh insights into historical genomic features coupled with Brassicaceae evolution and offer a potential model for broad-scale studies of adaptive radiation under an ever-changing environment.
文摘<i>Bacillus thuringiensis</i> (Bt) parasporal crystal proteins were well known to be toxic to certain insects and cytocidal activity against various human cancer cells. Bt serovar <i>coreanensis</i> ST7, non-pathogenic to insects and non-hemolytic, has an important parasporin, PS4Aa1 (Cry45Aa1), with potential toxicity to human cancer cells. In this study, we reported the feature of complete genome sequence and the cluster of orthologous groups of proteins function classification of ST7. Meanwhile, the evolutionary of ST7 was also studied. The genome data of ST7 will strongly contribute to a better understanding of the genomic diversity and evolution, and enrich the Bt genome database.
基金supported by the Self-supporting Program of Guangzhou Laboratory(SRPG22007)the CAS Research Fund(XDB38050200).
文摘The development of the term‘imaging genomics’.Despite significant advancements in human genomics,the phenotypic and clinical relevance of genomic features remains largely unknown.Imaging genomics,also known as radiogenomics,was proposed to find the associations between clinical image data and human genetic data,facilitating a better understanding of the molecular characteristics of diseases.Originally,imaging data are acquired mainly by Magnetic Resonance Imaging(MRI)for brain disease detection.
基金supported by the National Science Funds of China(No.82300219)the Natural Science Foundation of Shandong Province,China(Youth ProgramNo.ZR2023QH249).
文摘Digestive tract cancers(DTCs)are cancers that occur in the gastrointestinal tract and related organs,including esoph-ageal,gastric,and colorectal cancer.Since these types of cancer share similar endoderm developmental origins,the genomic and other molecular features can possess many similarities.Therefore,it is urgent to explore the com-monalities of molecular characteristics and signaling path-ways in the tumor microenvironment among these diseases.
