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Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma | Mammalian Genome
Description:
AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFκB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision .
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Keywords {🔍}
genes, google, scholar, insertions, article, cancer, cas, pubmed, insertion, tumors, tumor, identified, loci, ciss, vsts, gene, notch, akxd, expression, signaling, viral, cell, leukemia, strains, sequence, mouse, sites, mice, vst, screen, site, identify, single, proviral, retroviral, bcell, visa, common, human, lymphoid, data, genome, pathway, molecular, myeloid, evi, lymphomas, pcr, development, rate,
Topics {✒️}
^{{\delta {\rm{ct}}}} _{{{\rm{avg}}{\rm{ ^{{\delta {\rm{ct}}}} _{{{\rm{sample}}}} bcr-abl1-induced b-lymphoblastic leukemia org/pub/current_mus_musculus/data/fasta/dna/ t-cell lymphoma-prone akr/ remodeling carma1-bcl10-malt1 complexes ms-sql server databases long-range enhancer activity adult t-cell leukemia mln = mesenteric lymph node zinc-finger protein related real-time quantitative pcr b-cell lineage neoplasms t-cell antigen receptor single phenol/chloroform extraction hck protein-tyrosine kinases repeat-masked vst sequences mouse b-cell leukemia cell-cycle regulatory proteins inhibits e-protein activity article download pdf restriction-site-anchored primer false-positive error rate develop primarily b-cell restriction-site-specific primer mouse t-cell lymphomas high-throughput retroviral tagging slow-transforming retroviral mutagenesis background false-positive rate tumor-specific visa products wild-type mouse blood b-cell-specific genes true-positive insertions required b-cell lymphomas allowing mutate cellular proto-oncogenes existing cancer-predisposing mutations beta2 integrin-mediated early b-cell development develop b-cell tumors molecular tumor-typing information inbred mouse strains nested ltr-specific primer human acute leukemias normal b-cell development reducing false-positive detection /t-cell leukemia predominantly b-cell protein signaling identifies normal b-cell differentiation quantitative rt-pcr
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headline:Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma
description:AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFκB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at
http://www.mouse-genome.bcm.tmc.edu/vision
.
datePublished:2007-10-10T00:00:00Z
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Notch Signaling
Long Terminal Repeat
Recombinant Inbred
Notch Signaling Pathway
Lymphoid Tumor
Cell Biology
Animal Genetics and Genomics
Human Genetics
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headline:Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma
description:AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFκB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at
http://www.mouse-genome.bcm.tmc.edu/vision
.
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Notch Signaling
Long Terminal Repeat
Recombinant Inbred
Notch Signaling Pathway
Lymphoid Tumor
Cell Biology
Animal Genetics and Genomics
Human Genetics
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