التفاصيل البيبلوغرافية
| العنوان: |
Data from Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas |
| المؤلفون: |
Nathalie A. Johnson, Koren K. Mann, Roujun Peng, Qiang Pan-Hammarstrom, André Constantin, Errol Camlioglu, Madeleine Arseneault, Yasser Riazalhosseini, Celia Greenwood, Kathleen Klein Oros, Yury Monczak, Marco Albuquerque, Remi Froment, Pierre Sesques, Maryam Bayat, Caroline Rousseau, David MacDonald, Bruno M. Grande, Axel Tosikyan, Michael Crump, Tina Petrogiannis-Haliotis, Torsten Holm Nielsen, Kevin Bushell, Daniel Fornika, Stephen Yu, Jasleen Grewal, Lauren Chong, Rebecca L. Johnston, Arezoo Mohajeri, Miguel Alcaide, Sarit Assouline, Ryan D. Morin |
| بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
| سنة النشر: |
2023 |
| الوصف: |
Purpose: Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) is fatal in 90% of patients, and yet little is known about its biology.Experimental Design: Using exome sequencing, we characterized the mutation profiles of 38 rrDLBCL biopsies obtained at the time of progression after immunochemotherapy. To identify genes that may be associated with relapse, we compared the mutation frequency in samples obtained at relapse to an unrelated cohort of 138 diagnostic DLBCLs and separately amplified specific mutations in their matched diagnostic samples to identify clonal expansions.Results: On the basis of a higher frequency at relapse and evidence for clonal selection, TP53, FOXO1, MLL3 (KMT2C), CCND3, NFKBIZ, and STAT6 emerged as top candidate genes implicated in therapeutic resistance. We observed individual examples of clonal expansions affecting genes whose mutations had not been previously associated with DLBCL including two regulators of NF-κB: NFKBIE and NFKBIZ. We detected mutations that may be affect sensitivity to novel therapeutics, such as MYD88 and CD79B mutations, in 31% and 23% of patients with activated B-cell–type of rrDLBCL, respectively. We also identified recurrent STAT6 mutations affecting D419 in 36% of patients with the germinal center B (GCB) cell rrDLBCL. These were associated with activated JAK/STAT signaling, increased phospho-STAT6 protein expression and increased expression of STAT6 target genes.Conclusions: This work improves our understanding of therapeutic resistance in rrDLBCL and has identified novel therapeutic opportunities especially for the high-risk patients with GCB-type rrDLBCL. Clin Cancer Res; 22(9); 2290–300. ©2015 AACR. |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::23d8e7088123c06fa1735170d51d9bdc
https://doi.org/10.1158/1078-0432.c.6523535.v1 |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....23d8e7088123c06fa1735170d51d9bdc |
| قاعدة البيانات: |
OpenAIRE |
