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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-01-0169.
Submitted January 18, 2002
Accepted April 4, 2002
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*
Molecular Immunology Group, Tenovus Research Laboratory, Southampton University Hospitals, Southampton, United Kingdom
Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom
* Corresponding author; email: fs{at}soton.ac.uk.
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 VH genes. To determine an influence of tissue location, we assessed matched blood and splenic tumor cells from four 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, since several replacement mutations were located within or close to the CDRs, it raises the question of a role for antigen in driving tumor growth.
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