Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

M. Taskinen, R. Louhimo, S. Koivula, P. Chen, V. Rantanen, H. Holte, J. Delabie, M. L. Karjalainen-Lindsberg, M. Bjorkholm, O. Fluge, Lars Møller Pedersen, K. Fjorden, M. Jerkeman, M. Eriksson, S. Hautaniemi, S. Leppa

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. Results: We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion: COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL.
OriginalsprogEngelsk
Artikelnummere91031
TidsskriftP L o S One
Vol/bind9
Udgave nummer3
Antal sider11
ISSN1932-6203
DOI
StatusUdgivet - 2014

Citer dette

Taskinen, M., Louhimo, R., Koivula, S., Chen, P., Rantanen, V., Holte, H., ... Leppa, S. (2014). Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma. P L o S One, 9(3), [e91031]. https://doi.org/10.1371/journal.pone.0091031
Taskinen, M. ; Louhimo, R. ; Koivula, S. ; Chen, P. ; Rantanen, V. ; Holte, H. ; Delabie, J. ; Karjalainen-Lindsberg, M. L. ; Bjorkholm, M. ; Fluge, O. ; Pedersen, Lars Møller ; Fjorden, K. ; Jerkeman, M. ; Eriksson, M. ; Hautaniemi, S. ; Leppa, S. / Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma. I: P L o S One. 2014 ; Bind 9, Nr. 3.
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title = "Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma",
abstract = "Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. Results: We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion: COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL.",
author = "M. Taskinen and R. Louhimo and S. Koivula and P. Chen and V. Rantanen and H. Holte and J. Delabie and Karjalainen-Lindsberg, {M. L.} and M. Bjorkholm and O. Fluge and Pedersen, {Lars M{\o}ller} and K. Fjorden and M. Jerkeman and M. Eriksson and S. Hautaniemi and S. Leppa",
year = "2014",
doi = "10.1371/journal.pone.0091031",
language = "English",
volume = "9",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
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Taskinen, M, Louhimo, R, Koivula, S, Chen, P, Rantanen, V, Holte, H, Delabie, J, Karjalainen-Lindsberg, ML, Bjorkholm, M, Fluge, O, Pedersen, LM, Fjorden, K, Jerkeman, M, Eriksson, M, Hautaniemi, S & Leppa, S 2014, 'Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma', P L o S One, bind 9, nr. 3, e91031. https://doi.org/10.1371/journal.pone.0091031

Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma. / Taskinen, M.; Louhimo, R.; Koivula, S.; Chen, P.; Rantanen, V.; Holte, H.; Delabie, J.; Karjalainen-Lindsberg, M. L.; Bjorkholm, M.; Fluge, O.; Pedersen, Lars Møller; Fjorden, K.; Jerkeman, M.; Eriksson, M.; Hautaniemi, S.; Leppa, S.

I: P L o S One, Bind 9, Nr. 3, e91031, 2014.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

AU - Taskinen, M.

AU - Louhimo, R.

AU - Koivula, S.

AU - Chen, P.

AU - Rantanen, V.

AU - Holte, H.

AU - Delabie, J.

AU - Karjalainen-Lindsberg, M. L.

AU - Bjorkholm, M.

AU - Fluge, O.

AU - Pedersen, Lars Møller

AU - Fjorden, K.

AU - Jerkeman, M.

AU - Eriksson, M.

AU - Hautaniemi, S.

AU - Leppa, S.

PY - 2014

Y1 - 2014

N2 - Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. Results: We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion: COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL.

AB - Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. Results: We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion: COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL.

U2 - 10.1371/journal.pone.0091031

DO - 10.1371/journal.pone.0091031

M3 - Journal article

VL - 9

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 3

M1 - e91031

ER -