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Patterns of somatic mutations in VH genes reveal pathways of clonal transformation from MGUS to multiple myeloma

Patterns of somatic mutations in VH genes reveal pathways of clonal transformation from MGUS to multiple myeloma
Patterns of somatic mutations in VH genes reveal pathways of clonal transformation from MGUS to multiple myeloma
Monoclonal gammopathy of undetermined significance (MGUS) can transform to multiple myeloma (MM). In myeloma, mutated VH genes with sequence homogeneity reveal a postfollicular origin. Previously, some MGUS cases showed mutated VH genes with intraclonal variation, indicating an earlier stage of arrest. We investigated progression from 2 of 2 MGUS to MM, in which VH genes confirmed clonal evolution. In one MGUS case, intraclonal heterogeneity was evident, and transformation to myeloma occurred rapidly with apparent homogeneity in the emergent clone. However, residual MGUS-derived sequences were detectable at this time. Heterogeneity in MGUS does not associate with benign disease, but it indicates an origin from a tumorigenic cell, most likely surface immunoglobulin+, undergoing somatic mutation. The remaining case displayed intraclonal homogeneity at the MGUS stage, conceivably resulting from a self-cloning outgrowth from MGUS with heterogeneity. Transformation can occur at either MGUS stage, but it involves a single cell in which somatic mutation is then silent.
0006-4971
4137-4139
Zojer, Niklas
88a51a4d-0b56-4832-bc0f-f102fc49d656
Ludwig, Heinz
e1ea5005-de05-4940-a14c-4f1c8f54def9
Fiegl, Michael
c2b06fb6-2830-4bab-926e-a54c6b11d29b
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Sahota, Surinder S.
66c1457f-cba2-4c49-9c8c-fcee0748b6b8
Zojer, Niklas
88a51a4d-0b56-4832-bc0f-f102fc49d656
Ludwig, Heinz
e1ea5005-de05-4940-a14c-4f1c8f54def9
Fiegl, Michael
c2b06fb6-2830-4bab-926e-a54c6b11d29b
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Sahota, Surinder S.
66c1457f-cba2-4c49-9c8c-fcee0748b6b8

Zojer, Niklas, Ludwig, Heinz, Fiegl, Michael, Stevenson, Freda K. and Sahota, Surinder S. (2003) Patterns of somatic mutations in VH genes reveal pathways of clonal transformation from MGUS to multiple myeloma. Blood, 101 (10), 4137-4139. (doi:10.1182/blood-2002-09-2825).

Record type: Article

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) can transform to multiple myeloma (MM). In myeloma, mutated VH genes with sequence homogeneity reveal a postfollicular origin. Previously, some MGUS cases showed mutated VH genes with intraclonal variation, indicating an earlier stage of arrest. We investigated progression from 2 of 2 MGUS to MM, in which VH genes confirmed clonal evolution. In one MGUS case, intraclonal heterogeneity was evident, and transformation to myeloma occurred rapidly with apparent homogeneity in the emergent clone. However, residual MGUS-derived sequences were detectable at this time. Heterogeneity in MGUS does not associate with benign disease, but it indicates an origin from a tumorigenic cell, most likely surface immunoglobulin+, undergoing somatic mutation. The remaining case displayed intraclonal homogeneity at the MGUS stage, conceivably resulting from a self-cloning outgrowth from MGUS with heterogeneity. Transformation can occur at either MGUS stage, but it involves a single cell in which somatic mutation is then silent.

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More information

Published date: 2003
Additional Information: Neoplasia, brief report

Identifiers

Local EPrints ID: 26681
URI: http://eprints.soton.ac.uk/id/eprint/26681
ISSN: 0006-4971
PURE UUID: 7d0f823c-c583-4a63-8121-f9724f7d733a
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: Niklas Zojer
Author: Heinz Ludwig
Author: Michael Fiegl
Author: Surinder S. Sahota

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