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

Author:

Tran Thai Hoa1ORCID,Langlois Sylvie1,Meloche Caroline1,Caron Maxime1,St-Onge Pascal2ORCID,Rouette Alexandre1ORCID,Bataille Alain R.1ORCID,Jimenez-Cortes Camille1,Sontag Thomas1,Bittencourt Henrique1,Laverdière Caroline3,Lavallee Vincent-Philippe4ORCID,Leclerc Jean-Marie5,Cole Peter D6ORCID,Gennarini Lisa M.7,Kahn Justine M.8,Kelly Kara M.9,Michon Bruno10,Santiago Raoul11ORCID,Stevenson Kristen E.12,Welch Jennifer JG13ORCID,Schroeder Kaitlin12,Koch Victoria B.12,Cellot Sonia1,Silverman Lewis B12,Sinnett Daniel1

Affiliation:

1. CHU Sainte-Justine, Montreal, Canada

2. CHU Sainte-Justine, Montreal, Quebec, Canada

3. Hopital Sainte-Justine, Montreal, Canada

4. University of Montreal, Montreal, Qc, Canada

5. CHU Ste-Justine, Montreal, Canada

6. Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States

7. Children's Hospital at Montefiore, Bronx, New York, United States

8. Columbia University Medical Center, New York, New York, United States

9. Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States

10. Centre Hospitalier Universitaire de Québec, Québec City, Canada

11. Centre hospitalier de l'Université Laval, Quebec, Quebec, Canada

12. Dana-Farber Cancer Institute, Boston, Massachusetts, United States

13. Brown University, Providence, Rhode Island, United States

Abstract

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 following B-ALL subgroups: High hyperdiploid (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), PAX5 alterations (n=11), PAX5 P80R (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-seq identified several clinically-relevant genetic alterations not detected by conventional methods, supporting the integration of this technology in frontline pediatric ALL trials.

Publisher

American Society of Hematology

Subject

Hematology

Cited by 42 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3