Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP
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 b...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172218/ https://www.ncbi.nlm.nih.gov/pubmed/30287880 http://dx.doi.org/10.1038/s41598-018-33230-3 |
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author | Peroja, Pekka Pedersen, Mette Mantere, Tuomo Nørgaard, Peter Peltonen, Jenni Haapasaari, Kirsi-Maria Böhm, Jan Jantunen, Esa Turpeenniemi-Hujanen, Taina Rapakko, Katrin Karihtala, Peeter Soini, Ylermi Vasala, Kaija Kuittinen, Outi |
author_facet | Peroja, Pekka Pedersen, Mette Mantere, Tuomo Nørgaard, Peter Peltonen, Jenni Haapasaari, Kirsi-Maria Böhm, Jan Jantunen, Esa Turpeenniemi-Hujanen, Taina Rapakko, Katrin Karihtala, Peeter Soini, Ylermi Vasala, Kaija Kuittinen, Outi |
author_sort | Peroja, Pekka |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6172218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61722182018-10-05 Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP Peroja, Pekka Pedersen, Mette Mantere, Tuomo Nørgaard, Peter Peltonen, Jenni Haapasaari, Kirsi-Maria Böhm, Jan Jantunen, Esa Turpeenniemi-Hujanen, Taina Rapakko, Katrin Karihtala, Peeter Soini, Ylermi Vasala, Kaija Kuittinen, Outi Sci Rep Article 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. Nature Publishing Group UK 2018-10-04 /pmc/articles/PMC6172218/ /pubmed/30287880 http://dx.doi.org/10.1038/s41598-018-33230-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Peroja, Pekka Pedersen, Mette Mantere, Tuomo Nørgaard, Peter Peltonen, Jenni Haapasaari, Kirsi-Maria Böhm, Jan Jantunen, Esa Turpeenniemi-Hujanen, Taina Rapakko, Katrin Karihtala, Peeter Soini, Ylermi Vasala, Kaija Kuittinen, Outi Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP |
title | Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP |
title_full | Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP |
title_fullStr | Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP |
title_full_unstemmed | Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP |
title_short | Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP |
title_sort | mutation of tp53, translocation analysis and immunohistochemical expression of myc, bcl-2 and bcl-6 in patients with dlbcl treated with r-chop |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172218/ https://www.ncbi.nlm.nih.gov/pubmed/30287880 http://dx.doi.org/10.1038/s41598-018-33230-3 |
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