GRCh38 · COSMIC v100

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Reference

Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia.

Paper ID

COSP41798

Authors

Liu YF, Wang BY, Zhang WN, Huang JY, Li BS, Zhang M, Jiang L, Li JF, Wang MJ, Dai YJ, Zhang ZG, Wang Q, Kong J, Chen B, Zhu YM, Weng XQ, Shen ZX, Li JM, Wang J, Yan XJ, Li Y, Liang YM, Liu L, Chen XQ, Zhang WG, Yan JS, Hu JD, Shen SH, Chen J, Gu LJ, Pei D, Li Y, Wu G, Zhou X, Ren RB, Cheng C, Yang JJ, Wang KK, Wang SY, Zhang J, Mi JQ, Pui CH, Tang JY, Chen Z and Chen SJ

Affiliation

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China.

Journal

EBioMedicine, 2016;8:173-83
ISSN: 2352-3964
PMID: 27428428 (view at PubMed or Europe PMC)

Abstract

Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

Paper Status

Curated