Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma
Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequenci...
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2021
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oai:doaj.org-article:2d5795c274074d96834193cbf41542ef2021-12-02T14:07:47ZProposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma10.1038/s41598-020-80376-02045-2322https://doaj.org/article/2d5795c274074d96834193cbf41542ef2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80376-0https://doaj.org/toc/2045-2322Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.Lucía PedrosaIsmael Fernández-MirandaDavid Pérez-CallejoCristina QueroMarta RodríguezPaloma Martín-AcostaSagrario GómezJulia González-RincónAdrián SantosCarlos TarinJuan F. GarcíaFrancisco R. García-ArroyoAntonio RuedaFrancisca I. CamachoMónica García-CosíoAna HerederoMarta LlanosManuela MollejoMiguel Piris-VillaespesaJosé Gómez-CodinaNatalia Yanguas-CasásAntonio SánchezMiguel A. PirisMariano ProvencioMargarita Sánchez-BeatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q Lucía Pedrosa Ismael Fernández-Miranda David Pérez-Callejo Cristina Quero Marta Rodríguez Paloma Martín-Acosta Sagrario Gómez Julia González-Rincón Adrián Santos Carlos Tarin Juan F. García Francisco R. García-Arroyo Antonio Rueda Francisca I. Camacho Mónica García-Cosío Ana Heredero Marta Llanos Manuela Mollejo Miguel Piris-Villaespesa José Gómez-Codina Natalia Yanguas-Casás Antonio Sánchez Miguel A. Piris Mariano Provencio Margarita Sánchez-Beato Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma |
| description |
Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases. |
| format |
article |
| author |
Lucía Pedrosa Ismael Fernández-Miranda David Pérez-Callejo Cristina Quero Marta Rodríguez Paloma Martín-Acosta Sagrario Gómez Julia González-Rincón Adrián Santos Carlos Tarin Juan F. García Francisco R. García-Arroyo Antonio Rueda Francisca I. Camacho Mónica García-Cosío Ana Heredero Marta Llanos Manuela Mollejo Miguel Piris-Villaespesa José Gómez-Codina Natalia Yanguas-Casás Antonio Sánchez Miguel A. Piris Mariano Provencio Margarita Sánchez-Beato |
| author_facet |
Lucía Pedrosa Ismael Fernández-Miranda David Pérez-Callejo Cristina Quero Marta Rodríguez Paloma Martín-Acosta Sagrario Gómez Julia González-Rincón Adrián Santos Carlos Tarin Juan F. García Francisco R. García-Arroyo Antonio Rueda Francisca I. Camacho Mónica García-Cosío Ana Heredero Marta Llanos Manuela Mollejo Miguel Piris-Villaespesa José Gómez-Codina Natalia Yanguas-Casás Antonio Sánchez Miguel A. Piris Mariano Provencio Margarita Sánchez-Beato |
| author_sort |
Lucía Pedrosa |
| title |
Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma |
| title_short |
Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma |
| title_full |
Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma |
| title_fullStr |
Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma |
| title_full_unstemmed |
Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma |
| title_sort |
proposal and validation of a method to classify genetic subtypes of diffuse large b cell lymphoma |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/2d5795c274074d96834193cbf41542ef |
| work_keys_str_mv |
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