{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:14:29Z","timestamp":1761059669621,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T00:00:00Z","timestamp":1391472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007282","name":"UniBern Forschungsstiftung","doi-asserted-by":"crossref","award":["13\/2011"],"award-info":[{"award-number":["13\/2011"]}],"id":[{"id":"10.13039\/501100007282","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Werner and Hedy Berger-Janser Stiftung zur Erforschung der Krebskrankheiten","award":["2\/2010"],"award-info":[{"award-number":["2\/2010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>BCL2<\/jats:italic> is a target of somatic hypermutation in t(14;18) positive and also in a small fraction of t(14;18) negative diffuse large B\u2010cell lymphoma (DLBCL), suggesting an aberrant role of somatic hypermutation (ASHM). To elucidate the prevalence of <jats:italic>BCL2<\/jats:italic> mutations in lymphomas other than DLBCL, we Sanger\u2010sequenced the hypermutable region of the <jats:italic>BCL2<\/jats:italic> gene in a panel of 69 mature B\u2010cell lymphomas, including Richter's syndrome DLBCL, marginal\u2010zone lymphomas, post\u2010transplant lymphoproliferative disorders, HIV\u2010associated and common\u2010variable immunodeficiency\u2010associated DLBCL, all known to harbour ASHM\u2010dependent mutations in other genes, as well as 16 t(14,18) negative and 21 t(14;18) positive follicular lymphomas (FLs). We also investigated the pattern of <jats:italic>BCL2<\/jats:italic> mutations in longitudinal samples from 10 FL patients relapsing to FL or transforming to DLBCL (tFL). By direct sequencing, we found clonally represented <jats:italic>BCL2<\/jats:italic> mutations in 2\/16 (13%) of t(14;18) negative FLs, 2\/16 (13%) HIV\u2010DLBCLs, 1\/9 (11%) of Richter's syndrome DLBCL, 1\/17 (6%) of post\u2010transplant lymphoproliferative disorders and 1\/2 (50%) common\u2010variable immunodeficiency\u2010associated DLBCL. The proportion of mutated cases was significantly lower than in FLs carrying the t(14;18) translocation (15\/21, 71%). However, the absence of t(14;18) by FISH or PCR and the molecular features of the mutations strongly suggest that <jats:italic>BCL2<\/jats:italic> represents an additional target of ASHM in these entities. Analysis of the <jats:italic>BCL2<\/jats:italic> mutation pattern in clonally related FL\/FL and FL\/tFL samples revealed two distinct scenarios of genomic evolution: (i) direct evolution from the antecedent FL clone, with few novel clonal mutations acquired by the tFL major clone, and (ii) evolution from a common mutated long\u2010lived progenitor cell, which subsequently acquired distinct mutations in the FL and in the relapsed or transformed counterpart. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/hon.2132","type":"journal-article","created":{"date-parts":[[2014,2,5]],"date-time":"2014-02-05T03:34:53Z","timestamp":1391571293000},"page":"23-30","source":"Crossref","is-referenced-by-count":14,"title":["<i>BCL2<\/i> mutation spectrum in B\u2010cell non\u2010Hodgkin lymphomas and patterns associated with evolution of follicular lymphoma"],"prefix":"10.1002","volume":"33","author":[{"given":"Regula","family":"Burkhard","sequence":"first","affiliation":[{"name":"Experimental Oncology\/Hematology, Department of Clinical Research University of Bern  Bern Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Govind","family":"Bhagat","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center Columbia University Medical Center and New York Presbyterian Hospital  New York NY USA"},{"name":"Department of Pathology and Cell Biology Columbia University Medical Center and New York Presbyterian Hospital  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio B.","family":"Cogliatti","sequence":"additional","affiliation":[{"name":"Institute of Pathology State Hospital St. Gallen  St. Gallen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Rossi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine Amedeo Avogadro University of Eastern Piedmont  Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine Amedeo Avogadro University of Eastern Piedmont  Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Pasqualucci","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center Columbia University Medical Center and New York Presbyterian Hospital  New York NY USA"},{"name":"Department of Pathology and Cell Biology Columbia University Medical Center and New York Presbyterian Hospital  New York NY USA"},{"name":"Institute for Cancer Genetics Columbia University  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urban","family":"Novak","sequence":"additional","affiliation":[{"name":"Experimental Oncology\/Hematology, Department of Clinical Research University of Bern  Bern Switzerland"},{"name":"Department of Medical Oncology, Inselspital Bern University Hospital and University of Bern  Bern 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