{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:06:33Z","timestamp":1789880793107,"version":"4.0.1"},"reference-count":24,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>With the use of DNA-fiber fluorescent in situ hybridization, a BCL2 protein positive follicular lymphoma with a novel BCL2 breakpoint involving the immunoglobulin heavy chain (IGH) switch mu (S\u03bc) region instead of the JH orDH gene segments was identified. Sequence analysis showed that the genomic breakpoint is localized between the S\u03bc region of the IGH complex and the first intron of BCL2. Reverse-transcriptase polymerase chain reaction showed expression of a unique hybrid IGH-BCL2 transcript involving the transcription initiation site I\u03bc. Sequence analysis of the VH region of the functional nontranslocatedIGH allele showed multiple shared somatic mutations but also a high intraclonal variation (53 differences in 15 clones), compatible with the lymphoma cells staying in or re-entering the germinal center. This is the first example of a t(14;18) translocation that results from an illegitimate IGH class-switch recombination during the germinal center B-cell stage.<\/jats:p>","DOI":"10.1182\/blood.v99.2.716","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"716-718","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells"],"prefix":"10.1182","volume":"99","author":[{"given":"James A. L.","family":"Fenton","sequence":"first","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Willem","family":"Vaandrager","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelmina M.","family":"Aarts","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Bende","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Heering","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"van Dijk","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Morgan","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carel J. M.","family":"van Noesel","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed","family":"Schuuring","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Kluin","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Leiden University Medical Center, The Netherlands; Department of Haematology, University of Leeds, United Kingdom; Department of Pathology, University of Amsterdam, The Netherlands; Departments of Internal Medicine and Clinical Pathology, Groene Hart Hospital, Gouda, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021217050293100_B1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1093\/ajcp\/103.4.472","article-title":"Comparison of cytogenetic analysis, Southern analysis, and polymerase chain reaction for the detection of t(14; 18) in follicular lymphoma.","volume":"103","author":"Horsman","year":"1995","journal-title":"Am J Clin Pathol."},{"key":"2020021217050293100_B2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1182\/blood.V76.1.131.131","article-title":"Direct sequence analysis of the 14q+ and 18q\u2212 chromosome junctions in follicular lymphoma.","volume":"76","author":"Cotter","year":"1990","journal-title":"Blood."},{"key":"2020021217050293100_B3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/(SICI)1098-2264(200001)27:1<85::AID-GCC11>3.0.CO;2-9","article-title":"Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes.","volume":"27","author":"Vaandrager","year":"2000","journal-title":"Genes Chromsomes Cancer."},{"key":"2020021217050293100_B4","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1073\/pnas.86.8.2771","article-title":"Variant translocation of the BCL-2 gene in immunoglobulin \u03bb light chain gene in chronic lymphocytic leukemia.","volume":"86","author":"Adachi","year":"1989","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021217050293100_B5","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1182\/blood.V96.5.1947","article-title":"V(D)J recombinase-mediated transposition of the BCL2 gene to the IGH locus in follicular lymphoma.","volume":"96","author":"Vaandrager","year":"2000","journal-title":"Blood."},{"key":"2020021217050293100_B6","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1182\/blood.V84.5.1361.1361","article-title":"A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group.","volume":"84","author":"Harris","year":"1994","journal-title":"Blood."},{"key":"2020021217050293100_B7","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/sj.leu.2401465","article-title":"Isolation and characterisation of recombination events involving immunoglobulin heavy chain switch regions in multiple myeloma using long distance vectorette PCR (LDV-PCR).","volume":"13","author":"Proffitt","year":"1999","journal-title":"Leukemia."},{"key":"2020021217050293100_B8","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1182\/blood.V95.9.2922.009k38_2922_2929","article-title":"Variable heavy chain gene analysis of follicular lymphoma: correlation between heavy chain isotype expression and somatic mutation load.","volume":"95","author":"Aarts","year":"2000","journal-title":"Blood."},{"key":"2020021217050293100_B9","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1182\/blood.V85.12.3671.bloodjournal85123671","article-title":"Prognostic value of cellular proliferation and histologic grade in follicular lymphoma.","volume":"85","author":"Martin","year":"1995","journal-title":"Blood."},{"key":"2020021217050293100_B10","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.4049\/jimmunol.154.5.2237","article-title":"Secondary deletional recombination of rearranged switch region in Ig isotype-switched B cells: a mechanism for isotype stabilization.","volume":"154","author":"Zhang","year":"1995","journal-title":"J Immunol"},{"key":"2020021217050293100_B11","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1182\/blood.V77.7.1516.1516","article-title":"Patterns of chromosomal breakpoint locations in Burkitt's lymphoma: relevance to geography and Epstein-Barr virus association.","volume":"77","author":"Shiramizu","year":"1991","journal-title":"Blood."},{"key":"2020021217050293100_B12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/j.1460-2075.1988.tb02791.x","article-title":"Alternative promoters and exons, somatic mutations and deregulation of the Bcl-2-Ig fusion gene in lymphoma.","volume":"7","author":"Seto","year":"1988","journal-title":"EMBO J."},{"key":"2020021217050293100_B13","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/intimm\/6.4.491","article-title":"Expression of I mu-C gamma hybrid germline transcripts subsequent to immunoglobulin heavy chain class switching.","volume":"6","author":"Li","year":"1994","journal-title":"Int Immunol."},{"key":"2020021217050293100_B14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1074-7613(00)80432-X","article-title":"Within germinal centers, isotype switching of immunoglobulin genes occurs after the onset of somatic mutation.","volume":"4","author":"Liu","year":"1996","journal-title":"Immunity."},{"key":"2020021217050293100_B15","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1056\/NEJM199911113412007","article-title":"Cellular origins of B-cell lymphoma.","volume":"341","author":"Kuppers","year":"1999","journal-title":"N Engl J Med."},{"key":"2020021217050293100_B16","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1126\/science.278.5336.301","article-title":"V(D)J recombinase activity in a subset of germinal center B lymphocytes.","volume":"278","author":"Han","year":"1997","journal-title":"Science."},{"key":"2020021217050293100_B17","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/16933","article-title":"Secondary V(D)J recombination in B-1 cells.","volume":"397","author":"Qin","year":"1999","journal-title":"Nature."},{"key":"2020021217050293100_B18","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/23287","article-title":"Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization.","volume":"400","author":"Yu","year":"1999","journal-title":"Nature."},{"key":"2020021217050293100_B19","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1182\/blood.V96.3.808","article-title":"The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies.","volume":"96","author":"Willis","year":"2000","journal-title":"Blood."},{"key":"2020021217050293100_B20","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1182\/blood.V95.11.3520","article-title":"Follicular lymphomas' BCL-2\/IgH junctions contain templated nucleotide insertions: novel insights into the mechanism of t(14;18) translocation.","volume":"95","author":"Jager","year":"2000","journal-title":"Blood."},{"key":"2020021217050293100_B21","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1056\/NEJM198805263182106","article-title":"Activation of the c-myc oncogene in a precursor-B-cell blast crisis of follicular lymphoma, presenting as composite lymphoma.","volume":"318","author":"De Jong","year":"1988","journal-title":"N Engl J Med."},{"key":"2020021217050293100_B22","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/0161-5890(91)90118-4","article-title":"Early occurrence of immunoglobulin isotype switching in human fetal liver.","volume":"28","author":"Milili","year":"1991","journal-title":"Mol Immunol."},{"key":"2020021217050293100_B23","doi-asserted-by":"crossref","first-page":"13931","DOI":"10.1073\/pnas.93.24.13931","article-title":"Nardini E, Brents LA, Kirby SL, Kuehl WM. Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma.","volume":"93","author":"Bergsagel","year":"1996","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021217050293100_B24","doi-asserted-by":"crossref","first-page":"6209","DOI":"10.1002\/j.1460-2075.1995.tb00311.x","article-title":"Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma.","volume":"14","author":"Ye","year":"1995","journal-title":"EMBO J."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/99\/2\/716\/1679610\/h8020200716.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/99\/2\/716\/1679610\/h8020200716.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T20:12:12Z","timestamp":1682280732000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/99\/2\/716\/53355\/Follicular-lymphoma-with-a-novel-t1418-breakpoint"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1,15]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002,1,15]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v99.2.716","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2002,1,15]]}}}