Journal
BLOOD
Volume 118, Issue 11, Pages 3080-3087Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-03-341412
Keywords
-
Categories
Funding
- Children's Oncology Group [CA098543]
- National Cancer Institute [CA114762, U10 CA98413, U24 CA114766]
- National Institutes of Health Cancer Center [CA21765, CA118100]
- St Jude Children's Research Hospital
- University of New Mexico Cancer Center
- Leukemia & Lymphoma Society Specialized Center of Research [7388-06]
- CureSearch
- St Baldrick's Foundation
- National Health and Medical Research Council (Australia)
- American Lebanese Syrian Associated Charities of St Jude Children's Research Hospital
- National Cancer Institute, National Institutes of Health [N01-C0-12400]
Ask authors/readers for more resources
We sequenced 120 candidate genes in 187 high-risk childhood B-precursor acute lymphoblastic leukemias, the largest pediatric cancer genome sequencing effort reported to date. Integrated analysis of 179 validated somatic sequence mutations with genome-wide copy number alterations and gene expression profiles revealed a high frequency of recurrent somatic alterations in key signaling pathways, including B-cell development/differentiation (68% of cases), the TP53/RB tumor suppressor pathway (54%), Ras signaling (50%), and Janus kinases (11%). Recurrent mutations were also found in ETV6 (6 cases), TBL1XR1 (3), CREBBP (3), MUC4 (2), ASMTL (2), and ADARB2 (2). The frequency of mutations within the 4 major pathways varied markedly across genetic subtypes. Among 23 leukemias expressing a BCR-ABL1-like gene expression profile, 96% had somatic alterations in B-cell development/differentiation, 57% in JAK, and 52% in both pathways, whereas only 9% had Ras pathway mutations. In contrast, 21 cases defined by a distinct gene expression profile coupled with focal ERG deletion rarely had B-cell development/differentiation or JAK kinase alterations but had a high frequency (62%) of Ras signaling pathway mutations. These data extend the range of genes that are recurrently mutated in high-risk childhood B-precursor acute lymphoblastic leukemia and highlight important new therapeutic targets for selected patient subsets. (Blood. 2011; 118(11):3080-3087)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available