{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:38:22Z","timestamp":1790717902064,"version":"4.1.0"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,11,4]]},"abstract":"<jats:p>\n                    The search for target genes involved in unbalanced acquired chromosomal abnormalities has been largely unsuccessful, because the breakpoints of these rearrangements are too variable. Here, we use the example of dicentric chromosomes in B cell precursor acute lymphoblastic leukemia to show that, despite this heterogeneity, single genes are targeted through a variety of mechanisms. FISH showed that, although they were heterogeneous, breakpoints on 9p resulted in the partial or complete deletion of\n                    <jats:italic>PAX5<\/jats:italic>\n                    . Molecular copy number counting further delineated the breakpoints and facilitated cloning with long-distance inverse PCR. This approach identified 5 fusion gene partners with\n                    <jats:italic>PAX5<\/jats:italic>\n                    :\n                    <jats:italic>LOC392027<\/jats:italic>\n                    (7p12.1),\n                    <jats:italic>SLCO1B3<\/jats:italic>\n                    (12p12),\n                    <jats:italic>ASXL1<\/jats:italic>\n                    (20q11.1),\n                    <jats:italic>KIF3B<\/jats:italic>\n                    (20q11.21), and\n                    <jats:italic>C20orf112<\/jats:italic>\n                    (20q11.1). In each predicted fusion protein, the DNA-binding paired domain of\n                    <jats:italic>PAX5<\/jats:italic>\n                    was present. Using quantitative PCR, we demonstrated that both the deletion and gene fusion events resulted in the same underexpression of\n                    <jats:italic>PAX5<\/jats:italic>\n                    , which extended to the differential expression of the\n                    <jats:italic>PAX5<\/jats:italic>\n                    target genes,\n                    <jats:italic>EBF1<\/jats:italic>\n                    ,\n                    <jats:italic>ALDH1A1<\/jats:italic>\n                    ,\n                    <jats:italic>ATP9A<\/jats:italic>\n                    , and\n                    <jats:italic>FLT3<\/jats:italic>\n                    . Further molecular analysis showed deletion and mutation of the homologous\n                    <jats:italic>PAX5<\/jats:italic>\n                    allele, providing further support for the key role of\n                    <jats:italic>PAX5<\/jats:italic>\n                    . Here, we show that specific gene loci may be the target of heterogeneous translocation breakpoints in human cancer, acting through a variety of mechanisms. This approach indicates an application for the identification of cancer genes in solid tumours, where unbalanced chromosomal rearrangements are particularly prevalent and few genes have been identified. It can be extrapolated that this strategy will reveal that the same mechanisms operate in cancer pathogenesis in general.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0803494105","type":"journal-article","created":{"date-parts":[[2008,10,28]],"date-time":"2008-10-28T22:24:31Z","timestamp":1225232671000},"page":"17050-17054","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":70,"title":["Variable breakpoints target\n                    <i>PAX5<\/i>\n                    in patients with dicentric chromosomes: A model for the basis of unbalanced translocations in cancer"],"prefix":"10.1073","volume":"105","author":[{"given":"Qian","family":"An","sequence":"first","affiliation":[{"name":"Cancer Genomics and"},{"name":"Leukaemia Research Cytogenetics Groups, Cancer Sciences Division, University of Southampton, Southampton, SO16 6YD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Wright","sequence":"additional","affiliation":[{"name":"Cancer Genomics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb J.","family":"Konn","sequence":"additional","affiliation":[{"name":"Cancer Genomics and"},{"name":"Wessex Regional Genetic Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Matheson","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, University of Newcastle, Newcastle-upon-Tyne NE1 4LP, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Minto","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, University of Newcastle, Newcastle-upon-Tyne NE1 4LP, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony V.","family":"Moorman","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Groups, Cancer Sciences Division, University of Southampton, Southampton, SO16 6YD, United Kingdom;"},{"name":"Northern Institute for Cancer Research, University of Newcastle, Newcastle-upon-Tyne NE1 4LP, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Parker","sequence":"additional","affiliation":[{"name":"Cancer Genomics and"},{"name":"Leukaemia Research Cytogenetics Groups, Cancer Sciences Division, University of Southampton, Southampton, SO16 6YD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Griffiths","sequence":"additional","affiliation":[{"name":"West Midlands Regional Genetics Laboratory, Birmingham Women's Hospital, Birmingham B15 2TG, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona M.","family":"Ross","sequence":"additional","affiliation":[{"name":"Wessex Regional Genetic Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Davies","sequence":"additional","affiliation":[{"name":"Bristol Genetics Laboratory, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy G.","family":"Hall","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, University of Newcastle, Newcastle-upon-Tyne NE1 4LP, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine J.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Groups, Cancer Sciences Division, University of Southampton, Southampton, SO16 6YD, United Kingdom;"},{"name":"Northern Institute for Cancer Research, University of Newcastle, Newcastle-upon-Tyne NE1 4LP, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Irving","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, University of Newcastle, Newcastle-upon-Tyne NE1 4LP, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon C.","family":"Strefford","sequence":"additional","affiliation":[{"name":"Cancer Genomics and"},{"name":"Leukaemia Research Cytogenetics Groups, Cancer Sciences Division, University of Southampton, Southampton, SO16 6YD, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,11,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497supp-417"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2091"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1335"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V77.9.2016.2016"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V70.6.1962.1962"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870130109"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402923"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06328.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1159\/000106436"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05690"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/44076"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-025221"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06731.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-184"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth880"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1117679"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-088310"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.128"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6522707"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02643.x"},{"key":"e_1_3_3_21_2","volume-title":"An International System for Human Cytogenetic Nomenclature","year":"2005","unstructured":"An International System for Human Cytogenetic Nomenclature (S. 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