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.