Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma.
Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic...
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doaj-98e18833736b493c8cd158af3b9d62c82021-03-03T20:51:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01142e021281310.1371/journal.pone.0212813Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma.Julia González-RincónMiriam MéndezSagrario GómezJuan F GarcíaPaloma MartínCarmen BellasLucía PedrosaSocorro M Rodríguez-PinillaFrancisca I CamachoCristina QueroDavid Pérez-CallejoAntonio RuedaMarta LlanosJosé Gómez-CodinaMiguel A PirisSantiago Montes-MorenoCarmen BárcenaDelvys Rodríguez-AbreuJavier MenárguezLuis de la Cruz-MerinoSilvia MonsalvoConsuelo ParejoAna RoyuelaIvo KweeLuciano CascioneAlberto ArribasFrancesco BertoniManuela MollejoMariano ProvencioMargarita Sánchez-BeatoFollicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducted targeted massive parallel sequencing of 22 pre-transformed FL/transformed diffuse large B-cell lymphoma pairs and 20 diagnostic samples from non-transformed FL patients. Additionally, 22 matched samples from 11 transformed FL patients (pre-transformed FL and diffuse large B-cell lymphoma) and 9 non-transformed FLs were studied for copy number variation using SNP arrays. We identified recurrently mutated genes that were enriched at transformation, most notably LRP1B, GNA13 and POU2AF1, which have roles in B-cell differentiation, GC architecture and migration. Mutations in POU2AF1 might be associated with lower levels of expression, were more frequent in transformed FLs, and seemed to be specific to transformed- compared with de novo-diffuse large B-cell lymphomas. Pre-transformed FLs carried more mutations per sample and had greater subclonal heterogeneity than non-transformed FLs. Finally, we identified four mutated genes in FL samples that differed between patients who did and did not transform: NOTCH2, DTX1, UBE2A and HIST1H1E. The presence of mutations in these genes was associated with shorter time to transformation when mutated in the FL biopsies. This information might be useful for identifying patients at higher risk of transformation.https://doi.org/10.1371/journal.pone.0212813 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia González-Rincón Miriam Méndez Sagrario Gómez Juan F García Paloma Martín Carmen Bellas Lucía Pedrosa Socorro M Rodríguez-Pinilla Francisca I Camacho Cristina Quero David Pérez-Callejo Antonio Rueda Marta Llanos José Gómez-Codina Miguel A Piris Santiago Montes-Moreno Carmen Bárcena Delvys Rodríguez-Abreu Javier Menárguez Luis de la Cruz-Merino Silvia Monsalvo Consuelo Parejo Ana Royuela Ivo Kwee Luciano Cascione Alberto Arribas Francesco Bertoni Manuela Mollejo Mariano Provencio Margarita Sánchez-Beato |
spellingShingle |
Julia González-Rincón Miriam Méndez Sagrario Gómez Juan F García Paloma Martín Carmen Bellas Lucía Pedrosa Socorro M Rodríguez-Pinilla Francisca I Camacho Cristina Quero David Pérez-Callejo Antonio Rueda Marta Llanos José Gómez-Codina Miguel A Piris Santiago Montes-Moreno Carmen Bárcena Delvys Rodríguez-Abreu Javier Menárguez Luis de la Cruz-Merino Silvia Monsalvo Consuelo Parejo Ana Royuela Ivo Kwee Luciano Cascione Alberto Arribas Francesco Bertoni Manuela Mollejo Mariano Provencio Margarita Sánchez-Beato Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma. PLoS ONE |
author_facet |
Julia González-Rincón Miriam Méndez Sagrario Gómez Juan F García Paloma Martín Carmen Bellas Lucía Pedrosa Socorro M Rodríguez-Pinilla Francisca I Camacho Cristina Quero David Pérez-Callejo Antonio Rueda Marta Llanos José Gómez-Codina Miguel A Piris Santiago Montes-Moreno Carmen Bárcena Delvys Rodríguez-Abreu Javier Menárguez Luis de la Cruz-Merino Silvia Monsalvo Consuelo Parejo Ana Royuela Ivo Kwee Luciano Cascione Alberto Arribas Francesco Bertoni Manuela Mollejo Mariano Provencio Margarita Sánchez-Beato |
author_sort |
Julia González-Rincón |
title |
Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma. |
title_short |
Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma. |
title_full |
Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma. |
title_fullStr |
Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma. |
title_full_unstemmed |
Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma. |
title_sort |
unraveling transformation of follicular lymphoma to diffuse large b-cell lymphoma. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducted targeted massive parallel sequencing of 22 pre-transformed FL/transformed diffuse large B-cell lymphoma pairs and 20 diagnostic samples from non-transformed FL patients. Additionally, 22 matched samples from 11 transformed FL patients (pre-transformed FL and diffuse large B-cell lymphoma) and 9 non-transformed FLs were studied for copy number variation using SNP arrays. We identified recurrently mutated genes that were enriched at transformation, most notably LRP1B, GNA13 and POU2AF1, which have roles in B-cell differentiation, GC architecture and migration. Mutations in POU2AF1 might be associated with lower levels of expression, were more frequent in transformed FLs, and seemed to be specific to transformed- compared with de novo-diffuse large B-cell lymphomas. Pre-transformed FLs carried more mutations per sample and had greater subclonal heterogeneity than non-transformed FLs. Finally, we identified four mutated genes in FL samples that differed between patients who did and did not transform: NOTCH2, DTX1, UBE2A and HIST1H1E. The presence of mutations in these genes was associated with shorter time to transformation when mutated in the FL biopsies. This information might be useful for identifying patients at higher risk of transformation. |
url |
https://doi.org/10.1371/journal.pone.0212813 |
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