Sylvain Mareschal, Ph.D.
Bioinformatics engineer
January 27, 2021 at 15:59
Hayette et al, Hemasphere 2021
Hemasphere. 2021 Jan 27;5(2):e522.
doi: 10.1097/HS9.0000000000000522.

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

Sandrine Hayette, Béatrice Grange, Maxime Vallee, Claire Bardel, Sarah Huet, Isabelle Mosnier, Kaddour Chabane, Thomas Simonet, Marie Balsat, Maël Heiblig, Isabelle Tigaud, Franck E Nicolini, Sylvain Mareschal, Gilles Salles, Pierre Sujobert

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.

Pubmed, PMID: 33880432