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Amplification of 2p as a genomic marker for transformation in lymphoma

Kwiecinska, Anna LU ; Ichimura, Koichi ; Berglund, Mattias ; Dinets, Andrii ; Sulaiman, Luqman ; Collins, V. Peter ; Larsson, Catharina ; Porwit, Anna LU and Lagercrantz, Svetlana Bajalica (2014) In Genes Chromosomes and Cancer 53(9). p.750-768
Abstract

To outline further genetic mechanisms of transformation from follicular lymphoma (FL) to diffuse large B-cell lymphoma (DLBCL), we have performed whole genome array-CGH in 81 tumors from 60 patients [29 de novo DLBCL (dnDLBCL), 31 transformed DLBCL (tDLBCL), and 21 antecedent FL]. In 15 patients, paired tumor samples (primary FL and a subsequent tDLBCL) were available, among which three possessed more than two subsequent tumors, allowing us to follow specific genetic alterations acquired before, during, and after the transformation. Gain of 2p15-16.1 encompassing, among others, the REL, BCL11A, USP34, COMMD1, and OTX1 genes was found to be more common in the tDLBCL compared with dnDLBCL (P<0.001). Furthermore, a high-level... (More)

To outline further genetic mechanisms of transformation from follicular lymphoma (FL) to diffuse large B-cell lymphoma (DLBCL), we have performed whole genome array-CGH in 81 tumors from 60 patients [29 de novo DLBCL (dnDLBCL), 31 transformed DLBCL (tDLBCL), and 21 antecedent FL]. In 15 patients, paired tumor samples (primary FL and a subsequent tDLBCL) were available, among which three possessed more than two subsequent tumors, allowing us to follow specific genetic alterations acquired before, during, and after the transformation. Gain of 2p15-16.1 encompassing, among others, the REL, BCL11A, USP34, COMMD1, and OTX1 genes was found to be more common in the tDLBCL compared with dnDLBCL (P<0.001). Furthermore, a high-level amplification of 2p15-16.1 was also detected in the FL stage prior to transformation, indicating its importance during the transformation event. Quantitative real-time PCR showed a higher level of amplification of REL, USP34, and COMMD1 (all involved in the NFκΒ-pathway) compared with BCL11A, which indicates that the altered genes disrupting the NFκΒ pathway may be the driver genes of transformation rather than the previously suggested BCL11A. Moreover, a 17q21.33 amplification was exclusively found in tDLBCL, never in FL (P<0.04) or dnDLBCL, indicating an upregulation of genes of importance during the later phase of transformation. Taken together, our study demonstrates potential genomic markers for disease progression to clinically more aggressive forms. We also confirm the importance of the TP53-, CDKN2A-, and NFκΒ-pathways for the transformation from FL to DLBCL.

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author
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publishing date
type
Contribution to journal
publication status
published
subject
in
Genes Chromosomes and Cancer
volume
53
issue
9
pages
19 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:24832791
  • scopus:84904401423
ISSN
1045-2257
DOI
10.1002/gcc.22184
language
English
LU publication?
no
id
53af4d1a-0b83-4f21-b5f7-260ea8cd7929
date added to LUP
2019-05-22 09:49:32
date last changed
2024-04-16 08:35:03
@article{53af4d1a-0b83-4f21-b5f7-260ea8cd7929,
  abstract     = {{<p>To outline further genetic mechanisms of transformation from follicular lymphoma (FL) to diffuse large B-cell lymphoma (DLBCL), we have performed whole genome array-CGH in 81 tumors from 60 patients [29 de novo DLBCL (dnDLBCL), 31 transformed DLBCL (tDLBCL), and 21 antecedent FL]. In 15 patients, paired tumor samples (primary FL and a subsequent tDLBCL) were available, among which three possessed more than two subsequent tumors, allowing us to follow specific genetic alterations acquired before, during, and after the transformation. Gain of 2p15-16.1 encompassing, among others, the REL, BCL11A, USP34, COMMD1, and OTX1 genes was found to be more common in the tDLBCL compared with dnDLBCL (P&lt;0.001). Furthermore, a high-level amplification of 2p15-16.1 was also detected in the FL stage prior to transformation, indicating its importance during the transformation event. Quantitative real-time PCR showed a higher level of amplification of REL, USP34, and COMMD1 (all involved in the NFκΒ-pathway) compared with BCL11A, which indicates that the altered genes disrupting the NFκΒ pathway may be the driver genes of transformation rather than the previously suggested BCL11A. Moreover, a 17q21.33 amplification was exclusively found in tDLBCL, never in FL (P&lt;0.04) or dnDLBCL, indicating an upregulation of genes of importance during the later phase of transformation. Taken together, our study demonstrates potential genomic markers for disease progression to clinically more aggressive forms. We also confirm the importance of the TP53-, CDKN2A-, and NFκΒ-pathways for the transformation from FL to DLBCL.</p>}},
  author       = {{Kwiecinska, Anna and Ichimura, Koichi and Berglund, Mattias and Dinets, Andrii and Sulaiman, Luqman and Collins, V. Peter and Larsson, Catharina and Porwit, Anna and Lagercrantz, Svetlana Bajalica}},
  issn         = {{1045-2257}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{750--768}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes Chromosomes and Cancer}},
  title        = {{Amplification of 2p as a genomic marker for transformation in lymphoma}},
  url          = {{http://dx.doi.org/10.1002/gcc.22184}},
  doi          = {{10.1002/gcc.22184}},
  volume       = {{53}},
  year         = {{2014}},
}