Details

Autor(en) / Beteiligte

• 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

Titel

Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001

Ist Teil von

• Blood advances, 2022-02, Vol.6 (4), p.1329-1341

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• The molecular hallmark of childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent, prognostic genetic alterations, many of which are cryptic by conventional cytogenetics. RNA sequencing (RNA-seq) is a powerful next-generation sequencing technology that can 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 multicenter phase 3 clinical trial for children with newly diagnosed ALL. The Dana-Farber Cancer Institute ALL Consortium Protocol 16-001 enrolled 173 patients with ALL who consented to optional studies and had samples available for RNA-seq. RNA-seq identified at least 1 alteration in 157 patients (91%). 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 following B-cell ALL (B-ALL) subgroups: high hyperdiploid (n = 36), ETV6-RUNX1/-like (n = 31), TCF3-PBX1 (n = 7), KMT2A-rearranged (KMT2A-R; n = 5), intrachromosomal amplification of chromosome 21 (iAMP21) (n = 1), hypodiploid (n = 1), Philadelphia chromosome (Ph)-positive/Ph-like (n = 16), DUX4-R (n = 11), PAX5 alterations (PAX5 alt; n = 11), PAX5 P80R (n = 1), ZNF384-R (n = 4), NUTM1-R (n = 1), MEF2D-R (n = 1), and others (n = 10). RNA-seq identified 141 nonsynonymous mutations in 93 patients (54%); the most frequent were RAS-MAPK pathway mutations. Among 79 patients with both low-density array and RNA-seq data for the Philadelphia chromosome-like gene signature prediction, results were concordant in 74 patients (94%). In conclusion, RNA-seq identified several clinically relevant genetic alterations not detected by conventional methods, which supports the integration of this technology into front-line pediatric ALL trials. This trial was registered at www.clinicaltrials.gov as #NCT03020030. •RNA-seq is feasible in the context of a prospective clinical trial for de novo ALL within a clinically sensitive turnaround time.•RNA-seq identified several genetic alterations not detected by conventional methods that confer potential prognostic and therapeutic impact. [Display omitted]