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Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP

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Date
2018
Author(s)
Peroja, P
Pedersen, M
Mantere, T
Nørgaard, P
Peltonen, J
Haapasaari, KM
Böhm, J
Jantunen, E
Turpeenniemi-Hujanen, T
Rapakko, K
Karihtala, P
Soini, Y
Vasala, K
Kuittinen, O
Unique identifier
10.1038/s41598-018-33230-3
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Citation
Peroja, P. Pedersen, M. Mantere, T. Nørgaard, P. Peltonen, J. Haapasaari, KM. Böhm, J. Jantunen, E. Turpeenniemi-Hujanen, T. Rapakko, K. Karihtala, P. Soini, Y. Vasala, K. Kuittinen, O. (2018). Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP.  Scientific Reports, 8 (1) , 14814. 10.1038/s41598-018-33230-3.
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CC BY http://creativecommons.org/licenses/by/4.0/
Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with diverse outcomes. Concurrent translocation of MYC and BCL-2 and/or BCL-6, and concurrent immunohistochemical (IHC) high expression of MYC and BCL-2, have been linked to unfavorable treatment responses. TP53-mutated DLBCL has also been linked to worse outcome. Our aim was to evaluate the aforementioned issues in a cohort of 155 patients uniformly treated with R-CHOP-like therapies. We performed direct sequencing of TP53 exons 5, 6, 7 and 8 as well as fluorescence in-situ hybridization (FISH) of MYC, BCL-2 and BCL-6, and IHC of MYC, BCL-2 and BCL-6. In multivariate analysis, TP53 mutations in L3 and loop-sheet helix (LSH) associated with a risk ratio (RR) of disease-specific survival (DSS) of 8.779 (p = 0.022) and a RR of disease-free survival (DFS) of 10.498 (p = 0.011). In IHC analysis BCL-2 overexpression was associated with inferior DFS (p = 0.002) and DSS (p = 0.002). DLBCL with BCL-2 and MYC overexpression conferred inferior survival in all patients (DSS, p = 0.038 and DFS, p = 0.011) and in patients with non-GC phenotype (DSS (p = 0.013) and DFS (p = 0.010). Our results imply that in DLBCL, the location of TP53 mutations and IHC analysis of BCL-2 and MYC might have a role in the assessment of prognosis.

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https://erepo.uef.fi/handle/123456789/7080
Link to the original item
http://dx.doi.org/10.1038/s41598-018-33230-3
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Springer Nature America, Inc
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  • Terveystieteiden tiedekunta [1324]
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