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Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refrac...

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Autores principales: Park, Ha Young, Lee, Seung-Bok, Yoo, Hae-Yong, Kim, Seok-Jin, Kim, Won-Seog, Kim, Jong-Il, Ko, Young-Hyeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349924/
https://www.ncbi.nlm.nih.gov/pubmed/27835906
http://dx.doi.org/10.18632/oncotarget.13239
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author Park, Ha Young
Lee, Seung-Bok
Yoo, Hae-Yong
Kim, Seok-Jin
Kim, Won-Seog
Kim, Jong-Il
Ko, Young-Hyeh
author_facet Park, Ha Young
Lee, Seung-Bok
Yoo, Hae-Yong
Kim, Seok-Jin
Kim, Won-Seog
Kim, Jong-Il
Ko, Young-Hyeh
author_sort Park, Ha Young
collection PubMed
description Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refractory DLBCL, we conducted whole-exome sequencing and transcriptome sequencing for six patients with refractory and seven with responsive DLBCL. The average numbers of pathogenic somatic single nucleotide variants and indels in coding regions were 71 in refractory patients (range 28–120) and 38 (range 19–66) in responsive patients. Missense mutations of TP53 were exclusive in 50% (3/6) of refractory patients and involved the DNA-binding domain of TP53. All missense mutations of TP53 were accompanied by copy number deletions. RAB11FIP5, PRKCB, PRDM15, FNBP4, AHR, CEP128, BRE, DHX16, MYO6, and NMT1 mutations were recurrent in refractory patients. MYD88, B2M, SORCS3, and WDFY3 mutations were more frequent in refractory patients than in responsive patients. REL–BCL11A fusion was found in two refractory patients; one had both fusion and copy number gain. Recurrent copy gains of POU2AF1, SLC1A4, REL11, FANCL, CACNA1D, TRRAP, and CUX1 with significantly increased average expression were found in refractory patients. The expression profile revealed enriched gene sets associated with treatment resistance, including oxidative phosphorylation and ATP-binding cassette transporters. In conclusion, this study integrated both genomic and transcriptomic alterations associated with refractory DLBCL and found several treatment-resistance alterations that may contribute to refractoriness.
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spelling pubmed-53499242017-04-06 Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma Park, Ha Young Lee, Seung-Bok Yoo, Hae-Yong Kim, Seok-Jin Kim, Won-Seog Kim, Jong-Il Ko, Young-Hyeh Oncotarget Research Paper Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refractory DLBCL, we conducted whole-exome sequencing and transcriptome sequencing for six patients with refractory and seven with responsive DLBCL. The average numbers of pathogenic somatic single nucleotide variants and indels in coding regions were 71 in refractory patients (range 28–120) and 38 (range 19–66) in responsive patients. Missense mutations of TP53 were exclusive in 50% (3/6) of refractory patients and involved the DNA-binding domain of TP53. All missense mutations of TP53 were accompanied by copy number deletions. RAB11FIP5, PRKCB, PRDM15, FNBP4, AHR, CEP128, BRE, DHX16, MYO6, and NMT1 mutations were recurrent in refractory patients. MYD88, B2M, SORCS3, and WDFY3 mutations were more frequent in refractory patients than in responsive patients. REL–BCL11A fusion was found in two refractory patients; one had both fusion and copy number gain. Recurrent copy gains of POU2AF1, SLC1A4, REL11, FANCL, CACNA1D, TRRAP, and CUX1 with significantly increased average expression were found in refractory patients. The expression profile revealed enriched gene sets associated with treatment resistance, including oxidative phosphorylation and ATP-binding cassette transporters. In conclusion, this study integrated both genomic and transcriptomic alterations associated with refractory DLBCL and found several treatment-resistance alterations that may contribute to refractoriness. Impact Journals LLC 2016-11-09 /pmc/articles/PMC5349924/ /pubmed/27835906 http://dx.doi.org/10.18632/oncotarget.13239 Text en Copyright: © 2016 Park et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Park, Ha Young
Lee, Seung-Bok
Yoo, Hae-Yong
Kim, Seok-Jin
Kim, Won-Seog
Kim, Jong-Il
Ko, Young-Hyeh
Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma
title Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma
title_full Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma
title_fullStr Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma
title_full_unstemmed Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma
title_short Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma
title_sort whole-exome and transcriptome sequencing of refractory diffuse large b-cell lymphoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349924/
https://www.ncbi.nlm.nih.gov/pubmed/27835906
http://dx.doi.org/10.18632/oncotarget.13239
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