Rapidly developing sequencing technologies and bioinformatic approacheshave provided us with an unprecedented instrument allowing for an unbiased and exhaustive characterization of the cancer genome in genetic, epigen...Rapidly developing sequencing technologies and bioinformatic approacheshave provided us with an unprecedented instrument allowing for an unbiased and exhaustive characterization of the cancer genome in genetic, epigenetic and transcriptomic dimensions. This review introduces recent excitingfindings and new methodologies in genomic breast cancer research. With this development, cancer genome research will illuminate new delicate interactionsbetween molecular networks and thereby unravelthe underlying biological mechanisms for cancer initiation and progression. It also holds promise for providing a molecular clock for the estimation of the temporal processes of tumorigenesis. These methods in combination with single cell sequencing will make it possible to construct a family tree elucidating the evolutionary lineage relationships between cell populations at single-cell resolution. The anticipatedrapid progress in genomic breast cancer research should lead to anenhanced understanding of breast cancer biology andguide us towardsnovel ways to ultimatelyprevent and cure breast cancer.展开更多
Recombinant adeno-associated virus (rAAV) vectors have been extensively used for experimental gene therapy of inherited human diseases. Several advantages, such as simple vector construction, high targeting frequenc...Recombinant adeno-associated virus (rAAV) vectors have been extensively used for experimental gene therapy of inherited human diseases. Several advantages, such as simple vector construction, high targeting frequency by homologous recombination, and applica- bility to many cell types, make rAAV an attractive approach for targeted genome editing. Combined with cloning by somatic cell nuclear transfer (SCNT), this technology has recently been successfully adapted to generate gene-targeted pigs as models for cystic fibrosis, hereditary tyrosinemia type 1, and breast cancer. This review summarizes the development of rAAV for targeted genome editing in mammalian cells and provides strategies for enhancing the rAAV-mediated targeting frequency by homologous recombination. We discuss current development and application of the rAAV vectors for targeted genome editing in porcine primary fibroblasts, which are subse- quently used as donor cells for SCNT to generate cloned genetically designed pigs and provide positive perspectives for the generation of gene-targeted pigs with rAAV in the future.展开更多
Array comparative genomic hybridization (CGH) has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patien...Array comparative genomic hybridization (CGH) has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome (2GH arrays. A number of highly frequent genomic aberrations were discovered, which may act as "drivers" of tumor progression. Meanwhile, the genomic profiles of four "normal" breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.展开更多
CRISPR/Cas9 is an adaptive immunity system in bacteria and most archaea(Koonin and Makarova,2009;Horvath and Barrangou,2010).The CRISPR/Cas9 gene editing system is comprised of two key components,a small guide RNA(gRN...CRISPR/Cas9 is an adaptive immunity system in bacteria and most archaea(Koonin and Makarova,2009;Horvath and Barrangou,2010).The CRISPR/Cas9 gene editing system is comprised of two key components,a small guide RNA(gRNA)and a Cas9 endonuclease(Deltcheva etal.,2011;Jineketal.,2012).展开更多
文摘Rapidly developing sequencing technologies and bioinformatic approacheshave provided us with an unprecedented instrument allowing for an unbiased and exhaustive characterization of the cancer genome in genetic, epigenetic and transcriptomic dimensions. This review introduces recent excitingfindings and new methodologies in genomic breast cancer research. With this development, cancer genome research will illuminate new delicate interactionsbetween molecular networks and thereby unravelthe underlying biological mechanisms for cancer initiation and progression. It also holds promise for providing a molecular clock for the estimation of the temporal processes of tumorigenesis. These methods in combination with single cell sequencing will make it possible to construct a family tree elucidating the evolutionary lineage relationships between cell populations at single-cell resolution. The anticipatedrapid progress in genomic breast cancer research should lead to anenhanced understanding of breast cancer biology andguide us towardsnovel ways to ultimatelyprevent and cure breast cancer.
基金supported by the grants from the Danish National Researeh Infrastructure Programme to the Danish Genetieally Modified Animal Resource(DAG- MAR)as well as from the"Sino一Danish Breast Caneer Research Centre"under the ausPiees of the Danish National Researeh Foundation(Grundforskningsfonden)the National Natural Seience Foundation of China
文摘Recombinant adeno-associated virus (rAAV) vectors have been extensively used for experimental gene therapy of inherited human diseases. Several advantages, such as simple vector construction, high targeting frequency by homologous recombination, and applica- bility to many cell types, make rAAV an attractive approach for targeted genome editing. Combined with cloning by somatic cell nuclear transfer (SCNT), this technology has recently been successfully adapted to generate gene-targeted pigs as models for cystic fibrosis, hereditary tyrosinemia type 1, and breast cancer. This review summarizes the development of rAAV for targeted genome editing in mammalian cells and provides strategies for enhancing the rAAV-mediated targeting frequency by homologous recombination. We discuss current development and application of the rAAV vectors for targeted genome editing in porcine primary fibroblasts, which are subse- quently used as donor cells for SCNT to generate cloned genetically designed pigs and provide positive perspectives for the generation of gene-targeted pigs with rAAV in the future.
基金supported by the Danish Cancer Soci-ety through the budget of the Institute of Cancer Biol-ogy and by grants from the Danish Medical Research Council, the Natural and Medical Sciences Committee of the Danish Cancer Society, Novo Nordisk, the John and Birthe Meyer Foundation, the Solar Fonden, the Stensbygaard Fonden, the Kai Langeog Gundhild Kai Lange Fond, the will of Edith Stern, and the "Race Against Breast Cancer" ProjectThe support of the Marketing Department at the Danish Cancer Society is greatly appreciatedsupported by a project grant from the Hi-Tech Research and Development Program of China (2006AA02A301)
文摘Array comparative genomic hybridization (CGH) has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome (2GH arrays. A number of highly frequent genomic aberrations were discovered, which may act as "drivers" of tumor progression. Meanwhile, the genomic profiles of four "normal" breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.
基金This work was supported by the Lundbeck Foundation(R219-2016-1375 and R173-2014-1105)the Danish Research Council for Independent Research(DFF-1337-00128 and 9041-00317B)+4 种基金the Sapere Aude Young Research Talent Prize(DFF-1335-00763A)the Innovation Fund Denmark(BrainStem)Aarhus University Strategic Grant(AU-iCRISPR)the Sanming Project of Medicine in Shenzhen(SZ5M201612074)BGIResearch,and Guangdong Provincial Key Laboratory of Genome Read and Write(2017B030301011)。
文摘CRISPR/Cas9 is an adaptive immunity system in bacteria and most archaea(Koonin and Makarova,2009;Horvath and Barrangou,2010).The CRISPR/Cas9 gene editing system is comprised of two key components,a small guide RNA(gRNA)and a Cas9 endonuclease(Deltcheva etal.,2011;Jineketal.,2012).