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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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
_version_ 1783360897954086912
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
work_keys_str_mv AT perojapekka mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT pedersenmette mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT manteretuomo mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT nørgaardpeter mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT peltonenjenni mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT haapasaarikirsimaria mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT bohmjan mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT jantunenesa mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT turpeenniemihujanentaina mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT rapakkokatrin mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT karihtalapeeter mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT soiniylermi mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT vasalakaija mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop
AT kuittinenouti mutationoftp53translocationanalysisandimmunohistochemicalexpressionofmycbcl2andbcl6inpatientswithdlbcltreatedwithrchop