Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments

M. Perez, A. Pacchiarotti, M. Frontani, E. Pescarmona, E. Caprini, G. A. Lombardo, G. Russo, T. Faraggiana

Research output: Contribution to journalArticle

Abstract

Background Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies. Objectives This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL). Methods We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. Results We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1·6% to 21%, with a median rate of 9·8% and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12%) and VH4-59 (14%), were preferentially used in our case series. Conclusions Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.

Original languageEnglish
Pages (from-to)611-618
Number of pages8
JournalBritish Journal of Dermatology
Volume162
Issue number3
DOIs
Publication statusPublished - 2010

Fingerprint

Immunoglobulin Genes
B-Cell Lymphoma
Immunoglobulin Variable Region
Skin
Genes
B-Lymphocytes
Germinal Center
Antigens
Mutation
Lymphoma, Large B-Cell, Diffuse
Gene Rearrangement
Nucleic Acid Databases
Mutation Rate
Epitopes
Neoplasms
Leg
Databases
Pressure

Keywords

  • Clonal immunoglobulin rearrangements
  • Primary cutaneous B-cell lymphoma
  • Somatic mutations
  • VH gene usage

ASJC Scopus subject areas

  • Dermatology
  • Medicine(all)

Cite this

Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments. / Perez, M.; Pacchiarotti, A.; Frontani, M.; Pescarmona, E.; Caprini, E.; Lombardo, G. A.; Russo, G.; Faraggiana, T.

In: British Journal of Dermatology, Vol. 162, No. 3, 2010, p. 611-618.

Research output: Contribution to journalArticle

Perez, M. ; Pacchiarotti, A. ; Frontani, M. ; Pescarmona, E. ; Caprini, E. ; Lombardo, G. A. ; Russo, G. ; Faraggiana, T. / Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments. In: British Journal of Dermatology. 2010 ; Vol. 162, No. 3. pp. 611-618.
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abstract = "Background Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies. Objectives This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL). Methods We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. Results We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1·6{\%} to 21{\%}, with a median rate of 9·8{\%} and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39{\%} of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12{\%}) and VH4-59 (14{\%}), were preferentially used in our case series. Conclusions Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.",
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T1 - Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments

AU - Perez, M.

AU - Pacchiarotti, A.

AU - Frontani, M.

AU - Pescarmona, E.

AU - Caprini, E.

AU - Lombardo, G. A.

AU - Russo, G.

AU - Faraggiana, T.

PY - 2010

Y1 - 2010

N2 - Background Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies. Objectives This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL). Methods We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. Results We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1·6% to 21%, with a median rate of 9·8% and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12%) and VH4-59 (14%), were preferentially used in our case series. Conclusions Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.

AB - Background Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies. Objectives This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL). Methods We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. Results We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1·6% to 21%, with a median rate of 9·8% and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12%) and VH4-59 (14%), were preferentially used in our case series. Conclusions Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.

KW - Clonal immunoglobulin rearrangements

KW - Primary cutaneous B-cell lymphoma

KW - Somatic mutations

KW - VH gene usage

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