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  • 1
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    Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-12-15
    Description: Intratumoral heterogeneity arises through the evolution of genetically diverse subclones during tumor progression. However, it remains unknown whether cells within single genetic clones are functionally equivalent. By combining DNA copy number alteration (CNA) profiling, sequencing, and lentiviral lineage tracking, we followed the repopulation dynamics of 150 single lentivirus-marked lineages from 10 human colorectal cancers through serial xenograft passages in mice. CNA and mutational analysis distinguished individual clones and showed that clones remained stable upon serial transplantation. Despite this stability, the proliferation, persistence, and chemotherapy tolerance of lentivirally marked lineages were variable within each clone. Chemotherapy promoted the dominance of previously minor or dormant lineages. Thus, apart from genetic diversity, tumor cells display inherent functional variability in tumor propagation potential, which contributes to both cancer growth and therapy tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kreso, Antonija -- O'Brien, Catherine A -- van Galen, Peter -- Gan, Olga I -- Notta, Faiyaz -- Brown, Andrew M K -- Ng, Karen -- Ma, Jing -- Wienholds, Erno -- Dunant, Cyrille -- Pollett, Aaron -- Gallinger, Steven -- McPherson, John -- Mullighan, Charles G -- Shibata, Darryl -- Dick, John E -- R21 CA149990/CA/NCI NIH HHS/ -- R21CA149990-01/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):543-8. doi: 10.1126/science.1227670. Epub 2012 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Campbell Family Institute, Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23239622" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage ; Cell Tracking ; Clonal Evolution/*genetics ; Clone Cells ; Colorectal Neoplasms/*drug therapy/genetics/*pathology ; DNA Copy Number Variations ; Drug Resistance, Neoplasm/*genetics ; Humans ; Lentivirus ; Mice ; Neoplasm Transplantation ; Transcriptome ; Transduction, Genetic ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    MicroRNA expression in zebrafish embryonic development (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-05-28
    Description: MicroRNAs (miRNAs) are small noncoding RNAs, about 21 nucleotides in length, that can regulate gene expression by base-pairing to partially complementary mRNAs. Regulation by miRNAs can play essential roles in embryonic development. We determined the temporal and spatial expression patterns of 115 conserved vertebrate miRNAs in zebrafish embryos by microarrays and by in situ hybridizations, using locked-nucleic acid-modified oligonucleotide probes. Most miRNAs were expressed in a highly tissue-specific manner during segmentation and later stages, but not early in development, which suggests that their role is not in tissue fate establishment but in differentiation or maintenance of tissue identity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wienholds, Erno -- Kloosterman, Wigard P -- Miska, Eric -- Alvarez-Saavedra, Ezequiel -- Berezikov, Eugene -- de Bruijn, Ewart -- Horvitz, H Robert -- Kauppinen, Sakari -- Plasterk, Ronald H A -- New York, N.Y. -- Science. 2005 Jul 8;309(5732):310-1. Epub 2005 May 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hubrecht Laboratory, Centre for Biomedical Genetics, 3584 CT Utrecht, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15919954" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blotting, Northern ; Embryo, Nonmammalian/*metabolism ; Embryonic Development ; *Gene Expression ; In Situ Hybridization ; MicroRNAs/*genetics/*metabolism ; Multigene Family ; Oligonucleotide Array Sequence Analysis ; Oligonucleotide Probes ; Organ Specificity ; Time Factors ; Zebrafish/*embryology/*genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Target-selected inactivation of the zebrafish rag1 gene (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-07-06
    Description: The zebrafish has become a favorite organism for genetic analysis of vertebrate development, but methods for generating mutants by reverse genetic approaches have been lacking. We report a method to obtain stable mutants of a gene based on knowledge of the gene sequence only. Parental fish were mutagenized with N-ethyl-N-nitrosourea; in 2679 F1 fish, the rag1 gene was analyzed for heterozygous mutations by resequencing. In total, we found 15 mutations: 9 resulted in amino acid substitutions and 1 resulted in a premature stop codon. This truncation mutant was found to be homozygous viable and defective in V(D)J joining. Although presumably immune deficient, these homozygous rag1 mutant fish are able to reach adulthood and are fertile. As sperm samples from all 2679 F1 fish were collected and cryopreserved, we have in principle generated a mutant library from which mutants of most zebrafish genes can be isolated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wienholds, Erno -- Schulte-Merker, Stefan -- Walderich, Brigitte -- Plasterk, Ronald H A -- New York, N.Y. -- Science. 2002 Jul 5;297(5578):99-102.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12098699" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Codon, Terminator ; Ethylnitrosourea ; Female ; Gene Library ; Gene Rearrangement ; Genes, Immunoglobulin ; *Genes, RAG-1 ; Haplotypes ; Heterozygote ; Homeodomain Proteins/chemistry/genetics ; Immunoglobulin Heavy Chains/genetics ; Introns ; Male ; Mutagenesis ; *Mutation ; Mutation, Missense ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Recombination, Genetic ; Zebrafish/*genetics/immunology/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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