Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes

Pier Paolo Piccaluga; Giulia De Falco; Manjunath Kustagi; Anna Gazzola; Claudio Agostinelli; Claudio Tripodo; Eleonora Leucci; Anna Onnis; Annalisa Astolfi; Maria Rosaria Sapienza; Cristiana Bellan; Stefano Lazzi; Lynnette Tumwine; Michael Mawanda; Martin Ogwang; Valeria Calbi; Serena Formica; Andrea Califano; Stefano A Pileri; Lorenzo Leoncini

doi:10.1182/blood-2010-08-301556

Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes

Pier Paolo Piccaluga, Giulia De Falco, Manjunath Kustagi, Anna Gazzola, Claudio Agostinelli, Claudio Tripodo, Eleonora Leucci, Anna Onnis, Annalisa Astolfi, Maria Rosaria Sapienza, Cristiana Bellan, Stefano Lazzi, Lynnette Tumwine, Michael Mawanda, Martin Ogwang, Valeria Calbi, Serena Formica, Andrea Califano, Stefano A Pileri, Lorenzo Leoncini

96 Citations (Scopus)

Abstract

Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle control, B-cell receptor signaling, and tumor necrosis factor/nuclear factor κB pathways. Notably, by reverse engineering, we found that endemic and sporadic BLs diverged for genes dependent on RBL2 activity. Furthermore, we found that all BLs were intimately related to germinal center cells, differing from them for molecules involved in cell proliferation, immune response, and signal transduction. Finally, to validate GEP, we applied immunohistochemistry to a large panel of cases and showed that RBL2 can cooperate with MYC in inducing a neoplastic phenotype in vitro and in vivo. In conclusion, our study provided substantial insights on the pathobiology of BLs, by offering novel evidences that may be relevant for its classification and possibly future treatment.

Original language	English
Journal	Blood
Volume	117
Issue number	13
Pages (from-to)	3596-608
Number of pages	13
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2010-08-301556
Publication status	Published - 31 Mar 2011

Keywords

Animals
Burkitt Lymphoma
Cell Line, Tumor
Cluster Analysis
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
Microarray Analysis
Neoplasm Transplantation
Phenotype
Transplantation, Heterologous

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Piccaluga, P. P., De Falco, G., Kustagi, M., Gazzola, A., Agostinelli, C., Tripodo, C., Leucci, E., Onnis, A., Astolfi, A., Sapienza, M. R., Bellan, C., Lazzi, S., Tumwine, L., Mawanda, M., Ogwang, M., Calbi, V., Formica, S., Califano, A., Pileri, S. A., & Leoncini, L. (2011). Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes. Blood, 117(13), 3596-608. https://doi.org/10.1182/blood-2010-08-301556

Piccaluga, PP, De Falco, G, Kustagi, M, Gazzola, A, Agostinelli, C, Tripodo, C, Leucci, E, Onnis, A, Astolfi, A, Sapienza, MR, Bellan, C, Lazzi, S, Tumwine, L, Mawanda, M, Ogwang, M, Calbi, V, Formica, S, Califano, A, Pileri, SA & Leoncini, L 2011, 'Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes', Blood, vol. 117, no. 13, pp. 3596-608. https://doi.org/10.1182/blood-2010-08-301556

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title = "Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes",

abstract = "Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle control, B-cell receptor signaling, and tumor necrosis factor/nuclear factor κB pathways. Notably, by reverse engineering, we found that endemic and sporadic BLs diverged for genes dependent on RBL2 activity. Furthermore, we found that all BLs were intimately related to germinal center cells, differing from them for molecules involved in cell proliferation, immune response, and signal transduction. Finally, to validate GEP, we applied immunohistochemistry to a large panel of cases and showed that RBL2 can cooperate with MYC in inducing a neoplastic phenotype in vitro and in vivo. In conclusion, our study provided substantial insights on the pathobiology of BLs, by offering novel evidences that may be relevant for its classification and possibly future treatment.",

keywords = "Animals, Burkitt Lymphoma, Cell Line, Tumor, Cluster Analysis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Nude, Microarray Analysis, Neoplasm Transplantation, Phenotype, Transplantation, Heterologous",

author = "Piccaluga, {Pier Paolo} and {De Falco}, Giulia and Manjunath Kustagi and Anna Gazzola and Claudio Agostinelli and Claudio Tripodo and Eleonora Leucci and Anna Onnis and Annalisa Astolfi and Sapienza, {Maria Rosaria} and Cristiana Bellan and Stefano Lazzi and Lynnette Tumwine and Michael Mawanda and Martin Ogwang and Valeria Calbi and Serena Formica and Andrea Califano and Pileri, {Stefano A} and Lorenzo Leoncini",

year = "2011",

month = mar,

day = "31",

doi = "10.1182/blood-2010-08-301556",

language = "English",

volume = "117",

pages = "3596--608",

journal = "Blood",

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publisher = "American Society of Hematology",

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T1 - Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes

AU - Piccaluga, Pier Paolo

AU - De Falco, Giulia

AU - Kustagi, Manjunath

AU - Gazzola, Anna

AU - Agostinelli, Claudio

AU - Tripodo, Claudio

AU - Leucci, Eleonora

AU - Onnis, Anna

AU - Astolfi, Annalisa

AU - Sapienza, Maria Rosaria

AU - Bellan, Cristiana

AU - Lazzi, Stefano

AU - Tumwine, Lynnette

AU - Mawanda, Michael

AU - Ogwang, Martin

AU - Calbi, Valeria

AU - Formica, Serena

AU - Califano, Andrea

AU - Pileri, Stefano A

AU - Leoncini, Lorenzo

PY - 2011/3/31

Y1 - 2011/3/31

N2 - Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle control, B-cell receptor signaling, and tumor necrosis factor/nuclear factor κB pathways. Notably, by reverse engineering, we found that endemic and sporadic BLs diverged for genes dependent on RBL2 activity. Furthermore, we found that all BLs were intimately related to germinal center cells, differing from them for molecules involved in cell proliferation, immune response, and signal transduction. Finally, to validate GEP, we applied immunohistochemistry to a large panel of cases and showed that RBL2 can cooperate with MYC in inducing a neoplastic phenotype in vitro and in vivo. In conclusion, our study provided substantial insights on the pathobiology of BLs, by offering novel evidences that may be relevant for its classification and possibly future treatment.

AB - Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle control, B-cell receptor signaling, and tumor necrosis factor/nuclear factor κB pathways. Notably, by reverse engineering, we found that endemic and sporadic BLs diverged for genes dependent on RBL2 activity. Furthermore, we found that all BLs were intimately related to germinal center cells, differing from them for molecules involved in cell proliferation, immune response, and signal transduction. Finally, to validate GEP, we applied immunohistochemistry to a large panel of cases and showed that RBL2 can cooperate with MYC in inducing a neoplastic phenotype in vitro and in vivo. In conclusion, our study provided substantial insights on the pathobiology of BLs, by offering novel evidences that may be relevant for its classification and possibly future treatment.

KW - Animals

KW - Burkitt Lymphoma

KW - Cell Line, Tumor

KW - Cluster Analysis

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Mice

KW - Mice, Nude

KW - Microarray Analysis

KW - Neoplasm Transplantation

KW - Phenotype

KW - Transplantation, Heterologous

U2 - 10.1182/blood-2010-08-301556

DO - 10.1182/blood-2010-08-301556

M3 - Journal article

C2 - 21245480

SN - 0006-4971

VL - 117

SP - 3596

EP - 3608

JO - Blood

JF - Blood

IS - 13

ER -

Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes

Abstract

Keywords

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