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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-01-0169.

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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2659-2661

BRIEF REPORT

VH gene analysis of splenic marginal zone lymphomas reveals diversity in mutational status and initiation of somatic mutation in vivo

Delin Zhu, Jennifer Orchard, David G. Oscier, Dennis H. Wright, and Freda K. Stevenson

From the Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, United Kingdom; and the Department of Haematology, Royal Bournemouth Hospital, United Kingdom.

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.

© 2002 by The American Society of Hematology.
 

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  Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020