| Autor: |
Tran, Thai Hoa, Langlois, Sylvie, Meloche, Caroline, Caron, Maxime, Saint-Onge, Pascal, Rouette, Alexandre, Bataille, Alain R., Jimenez-Cortes, Camille, Sontag, Thomas, Bittencourt, Henrique, Laverdière, Caroline, Lavallée, Vincent-Philippe, Leclerc, Jean-Marie, Cole, Peter D., Gennarini, Lisa M., Kahn, Justine M., Kelly, Kara M., Michon, Bruno, Santiago, Raoul, Stevenson, Kristen E., Welch, Jennifer J.G., Schroeder, Kaitlin M., Koch, Victoria, Cellot, Sonia, Silverman, Lewis B., Sinnett, Daniel |
| Zdroj: |
Blood Advances; 20210101, Issue: Preprints |
| Abstrakt: |
The molecular hallmark of childhood ALL is characterized by recurrent, prognostic genetic alterations, many of which are cryptic by conventional cytogenetics. RNA-seq is a powerful next-generation sequencing technology with the ability to simultaneously identify cryptic gene rearrangements, sequence mutations and gene expression profiles in a single assay. We examined the feasibility and utility of incorporating RNA-seq into a prospective multi-center phase 3 clinical trial for children with newly-diagnosed ALL. Patients enrolled on the DFCI ALL Consortium Protocol 16-001 who consented to optional studies and had available material underwent RNA-seq. RNA-seq was performed in 173 ALL patients. RNA-seq identified at least one alteration in 157 (91%) patients. Fusion detection was 100% concordant with results obtained from conventional cytogenetic analyses. An additional 56 gene fusions were identified by RNA-seq, many of which confer prognostic or therapeutic significance. Gene expression profiling enabled further molecular classification into the followingB-ALL subgroups: Highhyperdiploid (n=36), ETV6-RUNX1/-like(n=31), TCF3-PBX1(n=7), KMT2A-rearranged (n=5), iAMP21 (n=1), hypodiploid (n=1), BCR-ABL1/-like (n=16), DUX4-rearranged (n=11), PAX5alterations (n=11), PAX5P80R (n=1), ZNF384-rearranged (n=4), NUTM1-rearranged (n=1), MEF2D-rearranged (n=1) and Others (n=10).RNA-seq identified 141 nonsynonymous mutations in 93 (54%) patients; the most frequent were RAS-MAPK pathway mutations. Among 79 patients with both low-density array and RNA-seq data for the Ph-like gene signature prediction, results were concordant in 74 (94%) patients. In conclusion, RNA-seqidentified several clinically-relevant genetic alterations not detected by conventional methods, supporting the integration of this technology in frontline pediatric ALL trials. |
| Databáze: |
Supplemental Index |
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