Cargando…

Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies

RNA sequencing holds great promise to improve the diagnostic of hematological malignancies, because this technique enables to detect fusion transcripts, to look for somatic mutations in oncogenes, and to capture transcriptomic signatures of nosological entities. However, the analytical performances...

Descripción completa

Detalles Bibliográficos
Autores principales: Hayette, Sandrine, Grange, Béatrice, Vallee, Maxime, Bardel, Claire, Huet, Sarah, Mosnier, Isabelle, Chabane, Kaddour, Simonet, Thomas, Balsat, Marie, Heiblig, Maël, Tigaud, Isabelle, Nicolini, Franck E., Mareschal, Sylvain, Salles, Gilles, Sujobert, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051993/
https://www.ncbi.nlm.nih.gov/pubmed/33880432
http://dx.doi.org/10.1097/HS9.0000000000000522
_version_ 1783679844152770560
author Hayette, Sandrine
Grange, Béatrice
Vallee, Maxime
Bardel, Claire
Huet, Sarah
Mosnier, Isabelle
Chabane, Kaddour
Simonet, Thomas
Balsat, Marie
Heiblig, Maël
Tigaud, Isabelle
Nicolini, Franck E.
Mareschal, Sylvain
Salles, Gilles
Sujobert, Pierre
author_facet Hayette, Sandrine
Grange, Béatrice
Vallee, Maxime
Bardel, Claire
Huet, Sarah
Mosnier, Isabelle
Chabane, Kaddour
Simonet, Thomas
Balsat, Marie
Heiblig, Maël
Tigaud, Isabelle
Nicolini, Franck E.
Mareschal, Sylvain
Salles, Gilles
Sujobert, Pierre
author_sort Hayette, Sandrine
collection PubMed
description RNA sequencing holds great promise to improve the diagnostic of hematological malignancies, because this technique enables to detect fusion transcripts, to look for somatic mutations in oncogenes, and to capture transcriptomic signatures of nosological entities. However, the analytical performances of targeted RNA sequencing have not been extensively described in diagnostic samples. Using a targeted panel of 1385 cancer-related genes in a series of 100 diagnosis samples and 8 controls, we detected all the already known fusion transcripts and also discovered unknown and/or unsuspected fusion transcripts in 12 samples. Regarding the analysis of transcriptomic profiles, we show that targeted RNA sequencing is performant to discriminate acute lymphoblastic leukemia entities driven by different oncogenic translocations. Additionally, we show that 86% of the mutations identified at the DNA level are also detectable at the messenger RNA (mRNA) level, except for nonsense mutations that are subjected to mRNA decay. We conclude that targeted RNA sequencing might improve the diagnosis of hematological malignancies. Standardization of the preanalytical steps and further refinements of the panel design and of the bioinformatical pipelines will be an important step towards its use in standard diagnostic procedures.
format Online
Article
Text
id pubmed-8051993
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-80519932021-04-19 Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies Hayette, Sandrine Grange, Béatrice Vallee, Maxime Bardel, Claire Huet, Sarah Mosnier, Isabelle Chabane, Kaddour Simonet, Thomas Balsat, Marie Heiblig, Maël Tigaud, Isabelle Nicolini, Franck E. Mareschal, Sylvain Salles, Gilles Sujobert, Pierre Hemasphere Article RNA sequencing holds great promise to improve the diagnostic of hematological malignancies, because this technique enables to detect fusion transcripts, to look for somatic mutations in oncogenes, and to capture transcriptomic signatures of nosological entities. However, the analytical performances of targeted RNA sequencing have not been extensively described in diagnostic samples. Using a targeted panel of 1385 cancer-related genes in a series of 100 diagnosis samples and 8 controls, we detected all the already known fusion transcripts and also discovered unknown and/or unsuspected fusion transcripts in 12 samples. Regarding the analysis of transcriptomic profiles, we show that targeted RNA sequencing is performant to discriminate acute lymphoblastic leukemia entities driven by different oncogenic translocations. Additionally, we show that 86% of the mutations identified at the DNA level are also detectable at the messenger RNA (mRNA) level, except for nonsense mutations that are subjected to mRNA decay. We conclude that targeted RNA sequencing might improve the diagnosis of hematological malignancies. Standardization of the preanalytical steps and further refinements of the panel design and of the bioinformatical pipelines will be an important step towards its use in standard diagnostic procedures. Lippincott Williams & Wilkins 2021-01-27 /pmc/articles/PMC8051993/ /pubmed/33880432 http://dx.doi.org/10.1097/HS9.0000000000000522 Text en Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Hayette, Sandrine
Grange, Béatrice
Vallee, Maxime
Bardel, Claire
Huet, Sarah
Mosnier, Isabelle
Chabane, Kaddour
Simonet, Thomas
Balsat, Marie
Heiblig, Maël
Tigaud, Isabelle
Nicolini, Franck E.
Mareschal, Sylvain
Salles, Gilles
Sujobert, Pierre
Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies
title Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies
title_full Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies
title_fullStr Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies
title_full_unstemmed Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies
title_short Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies
title_sort performances of targeted rna sequencing for the analysis of fusion transcripts, gene mutation, and expression in hematological malignancies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051993/
https://www.ncbi.nlm.nih.gov/pubmed/33880432
http://dx.doi.org/10.1097/HS9.0000000000000522
work_keys_str_mv AT hayettesandrine performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT grangebeatrice performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT valleemaxime performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT bardelclaire performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT huetsarah performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT mosnierisabelle performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT chabanekaddour performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT simonetthomas performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT balsatmarie performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT heibligmael performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT tigaudisabelle performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT nicolinifrancke performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT mareschalsylvain performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT sallesgilles performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies
AT sujobertpierre performancesoftargetedrnasequencingfortheanalysisoffusiontranscriptsgenemutationandexpressioninhematologicalmalignancies