Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ovarian non-Hodgkin's lymphomas (NHLs) are rare, and accurate diagnosis is frequently problematic. Previous studies have not provided either complete immunotypic or genotypic analyses. The authors report immunotyping and genotyping of three cases of ovarian NHL, including both primary and secondary types. Immunotyping disclosed all three were B-cell lymphomas composed of secretory blast stage lymphocytes showing kappa immunoglobulin (Ig) light chain clonal excess. DNA extracted from frozen tissue of each tumor was subjected to restriction endonuclease digestion and hybridized to probes for Ig genes, C kappa, C lambda, JH, and the T-cell receptor beta-chain gene. Rearrangements of the heavy chain and light chain Ig genes were observed in all three cases, confirming the monoclonal B-cell origin of the neoplastic population. No detectable rearrangements were observed in DNA extracted from three nonlymphoid ovarian tumors (dysgerminoma, granulosa cell tumor, and fibrothecoma). This study documents the potential value of immunotyping and genotypic analysis in the study of ovarian tumors.
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PMID:Immunotypic and genotypic characterization of non-Hodgkin's lymphomas of the ovary. 329 19

B-cell malignancies, such as human Burkitt's lymphoma, often contain translocations that link c-myc or other proto-oncogenes to the immunoglobulin heavy chain locus (IgH, encoded by Igh). The nature of elements that activate oncogenes within such translocations has been a long-standing question. Translocations within Igh involve DNA double-strand breaks initiated either by the RAG1/2 endonuclease during variable, diversity and joining gene segment (V(D)J) recombination, or by activation-induced cytidine deaminase (AID, also known as AICDA) during class switch recombination (CSR). V(D)J recombination in progenitor B (pro-B) cells assembles Igh variable region exons upstream of mu constant region (Cmu) exons, which are the first of several sets of C(H) exons ('C(H) genes') within a C(H) locus that span several hundred kilobases (kb). In mature B cells, CSR deletes Cmu and replaces it with a downstream C(H) gene. An intronic enhancer (iEmu) between the variable region exons and Cmu promotes V(D)J recombination in developing B cells. Furthermore, the Igh 3' regulatory region (Igh3'RR) lies downstream of the C(H) locus and modulates CSR by long-range transcriptional enhancement of C(H) genes. Transgenic mice bearing iEmu or Igh3'RR sequences fused to c-myc are predisposed to B lymphomas, demonstrating that such elements can confer oncogenic c-myc expression. However, in many B-cell lymphomas, Igh-c-myc translocations delete iEmu and place c-myc up to 200 kb upstream of the Igh3'RR. Here we address the oncogenic role of the Igh3'RR by inactivating it in two distinct mouse models for B-cell lymphoma with Igh-c-myc translocations. We show that the Igh3'RR is dispensable for pro-B-cell lymphomas with V(D)J recombination-initiated translocations, but is required for peripheral B-cell lymphomas with CSR-associated translocations. As the Igh3'RR is not required for CSR-associated Igh breaks or Igh-c-myc translocations in peripheral B-cell lymphoma progenitors, we conclude that this regulatory region confers oncogenic activity by long-range and developmental stage-specific activation of translocated c-myc genes.
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PMID:Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3' regulatory region. 2001 Jun 89