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Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas

Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas
Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas
Richter's syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma and is mostly represented by diffuse large B-cell lymphoma (DLBCL), with a post-germinal centre (GC) phenotype, clonally related to the pre-existing CLL. RS has a very poor prognosis and its pathogenetic mechanisms are poorly understood. In order to gain additional hints in RS pathogenesis, we performed a genome-wide DNA profiling study of 13 RS phases and eight matched CLL phases using the Affymetrix Human Mapping 250K NspI SNP arrays. Individual genomic profiles were heterogeneous, with no individual lesions occurring in more than half of the cases. However, several observations suggest that MYC pathway might be involved in RS. The 13q13.3-qter region containing MIRHG1 (MIR-17-92), a cluster of microRNA interacting with c-MYC, was acquired at the time of transformation. The 13q gain was coupled with the gain of c-MYC and loss of TP53. Translocation of c-MYC was acquired at transformation in a fraction of cases and this event appeared mutually exclusive with gain of MIRHG1. MYCN, a c-MYC homologue, was also recurrently gained. By comparing RS with 48 de novo DLBCL, RS presented a significantly lower prevalence of deletions affecting the PRDM1 and TNFAIP3, genes on 6q, known to be associated with a post-GC phenotype. In conclusion, the genomic profile of RS seems to differ from what observed in de novo DLBCL and in other transformed DLBCL. Genomic lesions occurring in RS are heterogeneous suggesting the existence of different RS subsets, possibly due to different transforming mechanisms. A deregulation of MYC pathway might represent one of the main transformation events in the pathogenesis of a subset of RS clonally related to the previous CLL.
lymphoma, myc, chronic lymphocytic leukaemia, 13q, 8q, affymetrix, MIRHG1
0278-0232
62-67
Scandurra, Marta
efda00b6-43e9-4a27-95ec-f35febddf5bb
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Deambrogi, Clara
c7d10651-681c-41b9-97b6-bf68f3c1243d
Rancoita, Paola M.V.
b8fac558-cb50-4233-b608-ad7e6432bbc3
Chigrinova, Ekaterina
3417cd52-82dd-4a3d-a354-69b69a3caace
Mian, Michael
faa8dc8b-d514-486b-9d6d-b045598381e3
Cerri, Michaela
59be0e0f-7336-4df6-ab05-52815a51a635
Rasi, Silvia
13639ced-c17f-4350-87e4-fb670cee592b
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Ponzoni, Maurilio
a7838e89-78cc-485c-a851-939ee6c12ed6
Moreno, Santiago M.
95c74560-01eb-4a7e-8698-95d760e08005
Piris, Miguel A.
e7806930-fbf2-4a2d-b53b-dd1d40df5bd0
Inghirami, Giorgio
d6810adb-392a-43cd-9ed3-434bb36aa4df
Zucca, Emanuele
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Gattei, Valter
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Rinaldi, Andrea
ae4d2559-25e9-47b8-8c77-308f6cb2a5c4
Kwee, Ivo
0926a658-8296-4ba4-9a70-abcf8a1aad96
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Bertoni, Francesco
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Scandurra, Marta
efda00b6-43e9-4a27-95ec-f35febddf5bb
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Deambrogi, Clara
c7d10651-681c-41b9-97b6-bf68f3c1243d
Rancoita, Paola M.V.
b8fac558-cb50-4233-b608-ad7e6432bbc3
Chigrinova, Ekaterina
3417cd52-82dd-4a3d-a354-69b69a3caace
Mian, Michael
faa8dc8b-d514-486b-9d6d-b045598381e3
Cerri, Michaela
59be0e0f-7336-4df6-ab05-52815a51a635
Rasi, Silvia
13639ced-c17f-4350-87e4-fb670cee592b
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Ponzoni, Maurilio
a7838e89-78cc-485c-a851-939ee6c12ed6
Moreno, Santiago M.
95c74560-01eb-4a7e-8698-95d760e08005
Piris, Miguel A.
e7806930-fbf2-4a2d-b53b-dd1d40df5bd0
Inghirami, Giorgio
d6810adb-392a-43cd-9ed3-434bb36aa4df
Zucca, Emanuele
40bd5950-d74e-4169-a2ea-0bfc1058058e
Gattei, Valter
df828ae8-1b40-4acb-8908-5a6b3d16cf99
Rinaldi, Andrea
ae4d2559-25e9-47b8-8c77-308f6cb2a5c4
Kwee, Ivo
0926a658-8296-4ba4-9a70-abcf8a1aad96
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Bertoni, Francesco
13297a2f-854a-4841-a410-d6bfca8afee8

Scandurra, Marta, Rossi, Davide, Deambrogi, Clara, Rancoita, Paola M.V., Chigrinova, Ekaterina, Mian, Michael, Cerri, Michaela, Rasi, Silvia, Sozzi, Elisa, Forconi, Francesco, Ponzoni, Maurilio, Moreno, Santiago M., Piris, Miguel A., Inghirami, Giorgio, Zucca, Emanuele, Gattei, Valter, Rinaldi, Andrea, Kwee, Ivo, Gaidano, Gianluca and Bertoni, Francesco (2010) Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas. Hematological Oncology, 28 (2), 62-67. (doi:10.1002/hon.932). (PMID:20014148)

Record type: Article

Abstract

Richter's syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma and is mostly represented by diffuse large B-cell lymphoma (DLBCL), with a post-germinal centre (GC) phenotype, clonally related to the pre-existing CLL. RS has a very poor prognosis and its pathogenetic mechanisms are poorly understood. In order to gain additional hints in RS pathogenesis, we performed a genome-wide DNA profiling study of 13 RS phases and eight matched CLL phases using the Affymetrix Human Mapping 250K NspI SNP arrays. Individual genomic profiles were heterogeneous, with no individual lesions occurring in more than half of the cases. However, several observations suggest that MYC pathway might be involved in RS. The 13q13.3-qter region containing MIRHG1 (MIR-17-92), a cluster of microRNA interacting with c-MYC, was acquired at the time of transformation. The 13q gain was coupled with the gain of c-MYC and loss of TP53. Translocation of c-MYC was acquired at transformation in a fraction of cases and this event appeared mutually exclusive with gain of MIRHG1. MYCN, a c-MYC homologue, was also recurrently gained. By comparing RS with 48 de novo DLBCL, RS presented a significantly lower prevalence of deletions affecting the PRDM1 and TNFAIP3, genes on 6q, known to be associated with a post-GC phenotype. In conclusion, the genomic profile of RS seems to differ from what observed in de novo DLBCL and in other transformed DLBCL. Genomic lesions occurring in RS are heterogeneous suggesting the existence of different RS subsets, possibly due to different transforming mechanisms. A deregulation of MYC pathway might represent one of the main transformation events in the pathogenesis of a subset of RS clonally related to the previous CLL.

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More information

e-pub ahead of print date: 13 December 2009
Published date: June 2010
Keywords: lymphoma, myc, chronic lymphocytic leukaemia, 13q, 8q, affymetrix, MIRHG1
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 358141
URI: http://eprints.soton.ac.uk/id/eprint/358141
ISSN: 0278-0232
PURE UUID: 578ac508-9926-4a04-b8ac-6e08e2595675
ORCID for Francesco Forconi: ORCID iD orcid.org/0000-0002-2211-1831

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Date deposited: 08 Oct 2013 11:31
Last modified: 15 Mar 2024 03:41

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Contributors

Author: Marta Scandurra
Author: Davide Rossi
Author: Clara Deambrogi
Author: Paola M.V. Rancoita
Author: Ekaterina Chigrinova
Author: Michael Mian
Author: Michaela Cerri
Author: Silvia Rasi
Author: Elisa Sozzi
Author: Maurilio Ponzoni
Author: Santiago M. Moreno
Author: Miguel A. Piris
Author: Giorgio Inghirami
Author: Emanuele Zucca
Author: Valter Gattei
Author: Andrea Rinaldi
Author: Ivo Kwee
Author: Gianluca Gaidano
Author: Francesco Bertoni

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