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V(H) gene analysis of splenic marginal zone lymphomas reveals diversity in mutational status and initiation of somatic mutation in vivo

V(H) gene analysis of splenic marginal zone lymphomas reveals diversity in mutational status and initiation of somatic mutation in vivo
V(H) gene analysis of splenic marginal zone lymphomas reveals diversity in mutational status and initiation of somatic mutation in vivo
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.
0006-4971
2659-2661
Zhu, Delin
49eeb78f-f607-4079-80b3-45574dc41fa5
Orchard, Jennifer
0e19209b-25ba-494b-b33e-61ce6fb12e27
Oscier, David G.
c2620a1d-25bb-48f7-9651-f5d023636381
Wright, Dennis H.
791e0346-8ff3-4d45-936f-665ca2e8b44c
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Zhu, Delin
49eeb78f-f607-4079-80b3-45574dc41fa5
Orchard, Jennifer
0e19209b-25ba-494b-b33e-61ce6fb12e27
Oscier, David G.
c2620a1d-25bb-48f7-9651-f5d023636381
Wright, Dennis H.
791e0346-8ff3-4d45-936f-665ca2e8b44c
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Zhu, Delin, Orchard, Jennifer, Oscier, David G., Wright, Dennis H. and Stevenson, Freda K. (2002) V(H) gene analysis of splenic marginal zone lymphomas reveals diversity in mutational status and initiation of somatic mutation in vivo. Blood, 100 (7), 2659-2661. (doi:10.1182/blood-2002-01-0169).

Record type: Article

Abstract

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.

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Published date: 2002

Identifiers

Local EPrints ID: 26676
URI: http://eprints.soton.ac.uk/id/eprint/26676
ISSN: 0006-4971
PURE UUID: 0e80de9d-9a1f-4935-86d1-03eef02618a9
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 24 Apr 2006
Last modified: 16 Mar 2024 02:54

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Contributors

Author: Delin Zhu
Author: Jennifer Orchard
Author: David G. Oscier
Author: Dennis H. Wright

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