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 language | English |
|---|---|
| Pages (from-to) | 611-618 |
| Number of pages | 8 |
| Journal | British Journal of Dermatology |
| Volume | 162 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2010 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=76949097528&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76949097528&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2133.2009.09576.x
DO - 10.1111/j.1365-2133.2009.09576.x
M3 - Article
C2 - 19906071
AN - SCOPUS:76949097528
VL - 162
SP - 611
EP - 618
JO - British Journal of Dermatology
JF - British Journal of Dermatology
SN - 0007-0963
IS - 3
ER -