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Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma.

Lawrie CH, Chi J, Taylor S, Tramonti D, Ballabio E, Palazzo S, Saunders NJ, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS - J. Cell. Mol. Med. (2008)

Bottom Line: Despite the indolent nature of FCL a significant proportion of cases undergo high-grade transformation to more aggressive DLBCL.In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases (n = 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation (n = 7) with FCL cases that had not transformed at a median follow-up of 60 months (n = 11).Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs (miR-223, 217, 222, 221 and let-7i and 7b) were found which could similarly predict or transformation in FCL (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. charles.lawrie@ndcls.ox.ac.uk

ABSTRACT
MicroRNAs are naturally occurring small RNA species that regulate gene expression and are frequently abnormally expressed in cancers. However, the role of microRNAs in lymphoma is poorly understood. Therefore, we undertook a comprehensive study of microRNA expression in two of the most common lymphomas: diffuse large B-cell lymphoma (DLBCL) (n = 80) and follicular lymphoma (FCL) (n = 18) using microarrays containing probes for 464 human microRNAs. Unsupervised cluster analysis revealed distinct expression patterns between these two lymphomas and specific microRNA signatures (including members of the miR-17-92 cluster) were derived that correctly predicted lymphoma type in >95% of cases. Furthermore, we identified microRNAs in de novo DLBCL (n = 64) associated with germinal centre-like and non-germinal centre-like immunophenotypes, international prognostic index status and event-free survival in CHOP and rituximab (R)-CHOP treated patients. Despite the indolent nature of FCL a significant proportion of cases undergo high-grade transformation to more aggressive DLBCL. In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases (n = 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation (n = 7) with FCL cases that had not transformed at a median follow-up of 60 months (n = 11). Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs (miR-223, 217, 222, 221 and let-7i and 7b) were found which could similarly predict or transformation in FCL (P < 0.05). These data suggest that microRNAs have potential as diagnostic and prognostic markers in these lymphomas and may be used to identify FCL patients at risk of high-grade transformation.

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(A) Unsupervised cluster analysis of purified lymphocyte subsets (n= 12), haematological cell lines (n= 40) and clinical cases of FCL and DLBCL (n= 98). Cluster analysis was carried out on human probe set (n= 464). (B) Cluster analysis of top 10 up- and down-regulated microRNAs differentially expressed between normal lymphocyte subsets and tumour samples (DLBCL and FCL).
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fig01: (A) Unsupervised cluster analysis of purified lymphocyte subsets (n= 12), haematological cell lines (n= 40) and clinical cases of FCL and DLBCL (n= 98). Cluster analysis was carried out on human probe set (n= 464). (B) Cluster analysis of top 10 up- and down-regulated microRNAs differentially expressed between normal lymphocyte subsets and tumour samples (DLBCL and FCL).

Mentions: Using unsupervised cluster analysis of the human probe set (n= 464) we found that the cell lines (n= 40), normal lymphocyte subsets (n= 12) and tumour samples (n= 98) have distinct microRNA profiles (Fig. 1A). Moreover, FCL and DLBCL clinical samples also generally clustered distinctly.


Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma.

Lawrie CH, Chi J, Taylor S, Tramonti D, Ballabio E, Palazzo S, Saunders NJ, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS - J. Cell. Mol. Med. (2008)

(A) Unsupervised cluster analysis of purified lymphocyte subsets (n= 12), haematological cell lines (n= 40) and clinical cases of FCL and DLBCL (n= 98). Cluster analysis was carried out on human probe set (n= 464). (B) Cluster analysis of top 10 up- and down-regulated microRNAs differentially expressed between normal lymphocyte subsets and tumour samples (DLBCL and FCL).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496139&req=5

fig01: (A) Unsupervised cluster analysis of purified lymphocyte subsets (n= 12), haematological cell lines (n= 40) and clinical cases of FCL and DLBCL (n= 98). Cluster analysis was carried out on human probe set (n= 464). (B) Cluster analysis of top 10 up- and down-regulated microRNAs differentially expressed between normal lymphocyte subsets and tumour samples (DLBCL and FCL).
Mentions: Using unsupervised cluster analysis of the human probe set (n= 464) we found that the cell lines (n= 40), normal lymphocyte subsets (n= 12) and tumour samples (n= 98) have distinct microRNA profiles (Fig. 1A). Moreover, FCL and DLBCL clinical samples also generally clustered distinctly.

Bottom Line: Despite the indolent nature of FCL a significant proportion of cases undergo high-grade transformation to more aggressive DLBCL.In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases (n = 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation (n = 7) with FCL cases that had not transformed at a median follow-up of 60 months (n = 11).Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs (miR-223, 217, 222, 221 and let-7i and 7b) were found which could similarly predict or transformation in FCL (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. charles.lawrie@ndcls.ox.ac.uk

ABSTRACT
MicroRNAs are naturally occurring small RNA species that regulate gene expression and are frequently abnormally expressed in cancers. However, the role of microRNAs in lymphoma is poorly understood. Therefore, we undertook a comprehensive study of microRNA expression in two of the most common lymphomas: diffuse large B-cell lymphoma (DLBCL) (n = 80) and follicular lymphoma (FCL) (n = 18) using microarrays containing probes for 464 human microRNAs. Unsupervised cluster analysis revealed distinct expression patterns between these two lymphomas and specific microRNA signatures (including members of the miR-17-92 cluster) were derived that correctly predicted lymphoma type in >95% of cases. Furthermore, we identified microRNAs in de novo DLBCL (n = 64) associated with germinal centre-like and non-germinal centre-like immunophenotypes, international prognostic index status and event-free survival in CHOP and rituximab (R)-CHOP treated patients. Despite the indolent nature of FCL a significant proportion of cases undergo high-grade transformation to more aggressive DLBCL. In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases (n = 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation (n = 7) with FCL cases that had not transformed at a median follow-up of 60 months (n = 11). Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs (miR-223, 217, 222, 221 and let-7i and 7b) were found which could similarly predict or transformation in FCL (P < 0.05). These data suggest that microRNAs have potential as diagnostic and prognostic markers in these lymphomas and may be used to identify FCL patients at risk of high-grade transformation.

Show MeSH
Related in: MedlinePlus