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.
