MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma

Charles H. Lawrie, Shamit Soneji, Teresa Marafioti, Christopher D O Cooper, Stefano Palazzo, Jennifer C. Paterson, Helen Cattan, Tariq Enver, Rachel Mager, Jacqueline Boultwood, James S. Wainscoat, Christian S R Hatton

Research output: Contribution to journalArticle

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Abstract

Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. This heterogeneous disease can be divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes by gene expression and immunohistochemical profiling. Using microarray analysis on prototypic cell lines, we identified microRNAs (miR-155, miR-21 and miR-221) that were more highly expressed in ABC-type than GCB-type cell lines. These microRNAs were over-expressed in de novo DLBCL (n = 35), transformed DLBCL (n = 14) and follicular center lymphoma cases (n = 27) compared to normal B cells. Consistent with the cell line model, expression levels were higher in DLBCL cases with an ABC-type immunophenotype than those that were GCB-type (p < 0.05). Moreover, using multivariate analysis we found that expression of miR-21 was an independent prognostic indicator in de novo DLBCL (p < 0.05). Interestingly, expression levels of both miR-155 and miR-21 were also higher in nonmalignant ABC than in GCB cells. As we also demonstrate that expression of microRNAs can be measured reliably from routine paraffin-embedded biopsies of more than 8-years-old (p < 0.001), we suggest that microRNAs could be clinically useful molecular markers for DLBCL as well as other cancers.

Original languageEnglish
Pages (from-to)1156-1161
Number of pages6
JournalInternational Journal of Cancer
Volume121
Issue number5
Early online date8 May 2007
DOIs
Publication statusPublished - 1 Sep 2007
Externally publishedYes

Fingerprint

Germinal Center
Lymphoma, Large B-Cell, Diffuse
MicroRNAs
B-Lymphocytes
Cell Line
Neoplasms
Follicular Lymphoma
Gene Expression Profiling
Microarray Analysis
Paraffin
Multivariate Analysis
Biopsy

Cite this

Lawrie, Charles H. ; Soneji, Shamit ; Marafioti, Teresa ; Cooper, Christopher D O ; Palazzo, Stefano ; Paterson, Jennifer C. ; Cattan, Helen ; Enver, Tariq ; Mager, Rachel ; Boultwood, Jacqueline ; Wainscoat, James S. ; Hatton, Christian S R. / MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. In: International Journal of Cancer. 2007 ; Vol. 121, No. 5. pp. 1156-1161.
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abstract = "Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40{\%} of all lymphoid tumors. This heterogeneous disease can be divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes by gene expression and immunohistochemical profiling. Using microarray analysis on prototypic cell lines, we identified microRNAs (miR-155, miR-21 and miR-221) that were more highly expressed in ABC-type than GCB-type cell lines. These microRNAs were over-expressed in de novo DLBCL (n = 35), transformed DLBCL (n = 14) and follicular center lymphoma cases (n = 27) compared to normal B cells. Consistent with the cell line model, expression levels were higher in DLBCL cases with an ABC-type immunophenotype than those that were GCB-type (p < 0.05). Moreover, using multivariate analysis we found that expression of miR-21 was an independent prognostic indicator in de novo DLBCL (p < 0.05). Interestingly, expression levels of both miR-155 and miR-21 were also higher in nonmalignant ABC than in GCB cells. As we also demonstrate that expression of microRNAs can be measured reliably from routine paraffin-embedded biopsies of more than 8-years-old (p < 0.001), we suggest that microRNAs could be clinically useful molecular markers for DLBCL as well as other cancers.",
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author = "Lawrie, {Charles H.} and Shamit Soneji and Teresa Marafioti and Cooper, {Christopher D O} and Stefano Palazzo and Paterson, {Jennifer C.} and Helen Cattan and Tariq Enver and Rachel Mager and Jacqueline Boultwood and Wainscoat, {James S.} and Hatton, {Christian S R}",
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Lawrie, CH, Soneji, S, Marafioti, T, Cooper, CDO, Palazzo, S, Paterson, JC, Cattan, H, Enver, T, Mager, R, Boultwood, J, Wainscoat, JS & Hatton, CSR 2007, 'MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma', International Journal of Cancer, vol. 121, no. 5, pp. 1156-1161. https://doi.org/10.1002/ijc.22800

MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. / Lawrie, Charles H.; Soneji, Shamit; Marafioti, Teresa; Cooper, Christopher D O; Palazzo, Stefano; Paterson, Jennifer C.; Cattan, Helen; Enver, Tariq; Mager, Rachel; Boultwood, Jacqueline; Wainscoat, James S.; Hatton, Christian S R.

In: International Journal of Cancer, Vol. 121, No. 5, 01.09.2007, p. 1156-1161.

Research output: Contribution to journalArticle

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T1 - MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma

AU - Lawrie, Charles H.

AU - Soneji, Shamit

AU - Marafioti, Teresa

AU - Cooper, Christopher D O

AU - Palazzo, Stefano

AU - Paterson, Jennifer C.

AU - Cattan, Helen

AU - Enver, Tariq

AU - Mager, Rachel

AU - Boultwood, Jacqueline

AU - Wainscoat, James S.

AU - Hatton, Christian S R

PY - 2007/9/1

Y1 - 2007/9/1

N2 - Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. This heterogeneous disease can be divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes by gene expression and immunohistochemical profiling. Using microarray analysis on prototypic cell lines, we identified microRNAs (miR-155, miR-21 and miR-221) that were more highly expressed in ABC-type than GCB-type cell lines. These microRNAs were over-expressed in de novo DLBCL (n = 35), transformed DLBCL (n = 14) and follicular center lymphoma cases (n = 27) compared to normal B cells. Consistent with the cell line model, expression levels were higher in DLBCL cases with an ABC-type immunophenotype than those that were GCB-type (p < 0.05). Moreover, using multivariate analysis we found that expression of miR-21 was an independent prognostic indicator in de novo DLBCL (p < 0.05). Interestingly, expression levels of both miR-155 and miR-21 were also higher in nonmalignant ABC than in GCB cells. As we also demonstrate that expression of microRNAs can be measured reliably from routine paraffin-embedded biopsies of more than 8-years-old (p < 0.001), we suggest that microRNAs could be clinically useful molecular markers for DLBCL as well as other cancers.

AB - Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. This heterogeneous disease can be divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes by gene expression and immunohistochemical profiling. Using microarray analysis on prototypic cell lines, we identified microRNAs (miR-155, miR-21 and miR-221) that were more highly expressed in ABC-type than GCB-type cell lines. These microRNAs were over-expressed in de novo DLBCL (n = 35), transformed DLBCL (n = 14) and follicular center lymphoma cases (n = 27) compared to normal B cells. Consistent with the cell line model, expression levels were higher in DLBCL cases with an ABC-type immunophenotype than those that were GCB-type (p < 0.05). Moreover, using multivariate analysis we found that expression of miR-21 was an independent prognostic indicator in de novo DLBCL (p < 0.05). Interestingly, expression levels of both miR-155 and miR-21 were also higher in nonmalignant ABC than in GCB cells. As we also demonstrate that expression of microRNAs can be measured reliably from routine paraffin-embedded biopsies of more than 8-years-old (p < 0.001), we suggest that microRNAs could be clinically useful molecular markers for DLBCL as well as other cancers.

KW - Diffuse large B cell lymphoma

KW - Follicular center lymphoma

KW - Microarray

KW - microRNA

KW - Prognosis

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