{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:31:16Z","timestamp":1791117076180,"version":"4.1.0"},"reference-count":22,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,10,1]]},"abstract":"<jats:p>Tumors of the splenic marginal zone can present in spleen or blood. The maturational status of the neoplastic B cells from each site appears heterogeneous, with either unmutated or mutated variable-region heavy chain (VH) genes. To determine an influence of tissue location, we assessed matched blood and splenic tumor cells from 4 patients and found them identical. However, one patient with unmutated VH genes in blood and spleen developed a clonally related diffuse large B-cell lymphoma in the chest wall. Strikingly, this subclone had undergone significant somatic mutation, with clear intraclonal heterogeneity. To our knowledge, this is the first case of a B-cell tumor showing initiation of somatic mutation in vivo. The finding emphasizes that the tissue microenvironment can influence tumor cell behavior and possibly affect disease progression. Importantly, because several replacement mutations were located within or close to the complementarity-determining regions (CDRs), it raises the question of a role for antigen in driving tumor growth.<\/jats:p>","DOI":"10.1182\/blood-2002-01-0169","type":"journal-article","created":{"date-parts":[[2002,9,18]],"date-time":"2002-09-18T16:26:06Z","timestamp":1032366366000},"page":"2659-2661","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":39,"title":["V H gene analysis of splenic marginal zone lymphomas reveals diversity in mutational status and initiation of somatic mutation in vivo"],"prefix":"10.1182","volume":"100","author":[{"given":"Delin","family":"Zhu","sequence":"first","affiliation":[{"name":"From the Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, United Kingdom; and the Department of Haematology, Royal Bournemouth Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Orchard","sequence":"additional","affiliation":[{"name":"From the Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, United Kingdom; and the Department of Haematology, Royal Bournemouth Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Oscier","sequence":"additional","affiliation":[{"name":"From the Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, United Kingdom; and the Department of Haematology, Royal Bournemouth Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis H.","family":"Wright","sequence":"additional","affiliation":[{"name":"From the Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, United Kingdom; and the Department of Haematology, Royal Bournemouth Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freda K.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"From the Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, United Kingdom; and the Department of Haematology, Royal Bournemouth Hospital, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2019111822215552400_B1","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1097\/00000478-200110000-00007","article-title":"Progression to large B-cell lymphoma in splenic marginal zone lymphoma: a description of a series of 12 cases.","volume":"25","author":"Camacho","year":"2001","journal-title":"Am J Surg Pathol."},{"key":"2019111822215552400_B2","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1182\/blood.V85.6.1603.bloodjournal8561603","article-title":"Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes.","volume":"85","author":"Zhu","year":"1995","journal-title":"Blood."},{"key":"2019111822215552400_B3","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0046-8177(98)80007-5","article-title":"Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation.","volume":"29","author":"Dunn-Walters","year":"1998","journal-title":"Hum Pathol."},{"key":"2019111822215552400_B4","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1182\/blood.V91.7.2381","article-title":"Mutation analysis of the rearranged immunoglobulin heavy chain genes of marginal zone cell lymphomas indicates an origin from different marginal zone B lymphocyte subsets.","volume":"91","author":"Tierens","year":"1998","journal-title":"Blood."},{"key":"2019111822215552400_B5","first-page":"135","volume-title":"World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues.","author":"Jaffe","year":"2001"},{"key":"2019111822215552400_B6","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1182\/blood.V83.11.3279.3279","article-title":"Idiotypic vaccination against human B-cell lymphoma: rescue of variable region gene sequences from biopsy material for assembly as single-chain Fv personal vaccines.","volume":"83","author":"Hawkins","year":"1994","journal-title":"Blood."},{"key":"2019111822215552400_B7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0167-5699(95)80166-9","article-title":"The human immunoglobulin VH repertoire.","volume":"16","author":"Cook","year":"1995","journal-title":"Immunol Today."},{"key":"2019111822215552400_B8","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1182\/blood.V94.6.1848","article-title":"Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. 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