![]() ![]() High-throughput retroviral tagging to identify components of specific signaling pathways in cancer. ![]() Genome-wide retroviral insertional tagging of cancer genes in Cdkn2a-deficient mice. Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias. Nakamura, T., Largaespada, D.A., Shaughnessy, J.D. The Hedgehog and Wnt signalling pathways in cancer. Loss of heterozygosity and reduced expression of the CUTL1 gene in uterine leiomyomas. ![]() Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma. Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17. The involvement of the candidate proto-oncogene NFKB2/ lyt-10 in lymphoid malignancies. Neri, A., Fracchiolla, N.S., Migliazza, A., Trecca, D. Characterization of colorectal-cancer-related cDNA clones obtained by subtractive hybridization screening. The B-lymphocyte maturation promoting transcription factor BLIMP1/PRDI-BF1 maps to D6S447 on human chromosome 6q21-q22.1 and the syntenic region of mouse chromosome 10. Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels. Insertional inactivation of the p53 gene during friend leukemia: a new strategy for identifying tumor suppressor genes. Breakpoints of Burkitt's lymphoma t(8 22) translocations map within a distance of 300 kb downstream of MYC. Long-distance activation of the Myc protooncogene by provirus insertion in Mlvi-1 or Mlvi-4 in rat T-cell lymphomas. Accelerated appearance of multiple B cell lymphoma types in NFS/N mice congenic for ecotropic murine leukemia viruses. Genetic profile of insertion mutations in mouse leukemias and lymphomas. Leukaemia disease genes: large-scale cloning and pathway predictions. Our studies demonstrate the power of retroviral tagging for cancer gene discovery in the post-genome era and indicate a largely unrecognized complexity in mouse and presumably human cancer. Thirty-six CISs encode genes that are known or predicted to be genes involved in human cancer or their homologs, whereas others encode candidate genes that have not yet been examined for a role in human cancer. These studies identified 152 loci that are targets of retroviral integration in more than one tumor (common retroviral integration sites, CISs) and therefore likely to encode a cancer gene. We then compared these sequences, and another 415 RIS sequences previously cloned from BXH2 myeloid leukemias and from a few AKXD lymphomas, against the recently assembled mouse genome sequence. Using high throughput inverse PCR 1, we cloned and analyzed the sequences of 884 RISs from a tumor panel composed primarily of B-cell lymphomas. Here we report the first large-scale use of retroviral tagging for cancer gene discovery in the post-genome era. The retroviral integration sites (RISs) in these tumors thus provide powerful genetic tags for the discovery of genes involved in cancer 1, 2. Retroviral insertional mutagenesis in BXH2 and AKXD mice induces a high incidence of myeloid leukemia and B- and T-cell lymphoma, respectively. ![]()
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