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Nat Genet. 2015 Nov;47(11):1326-1333. doi: 10.1038/ng.3400. Epub 2015 Oct 12.

The genomic landscape of juvenile myelomonocytic leukemia.

Author information

1
Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA.
2
Broad Institute of MIT and Harvard, Cambridge, MA.
3
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN.
4
Department of Neurological Surgery, University of California, San Francisco, CA.
5
Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN.
6
Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA.
7
Department of Pediatrics, The Johns Hopkins Hospital, Baltimore, MA.
8
Department of Pediatrics, Emory University School of Medicine, Aflac Cancer and Blood Disorder Center, Atlanta, GA.
9
Department of Pediatrics, Texas Tech University, El Paso, TX.
10
Department of Pediatrics, Seattle Children's Hospital, Seattle, WA.
11
Department of Pediatrics, Stanford School of Medicine, Stanford, CA.
12
Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR.
13
Department of Pediatric Hematology Oncology, University of Utah, Salt Lake City, UT.
14
Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.
15
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
16
Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
17
Pediatric Hematology Oncology, SSM Cardinal Glennon Children's Medical Center, Saint Louis, MO.
18
Division of Pediatric Hematology Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN.
19
Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
20
Pediatric Hematology Oncology, Pediatric Specialists of Lehigh Valley Hospital, Bethlehem, PA.
21
Pediatric Bone Marrow Transplant Program, Oregon Health & Science University, Portland, OR.
22
Department of Pediatrics, University of North Carolina at Chapel Hill, NC.
23
Division of Pediatric Oncology, Children's National Medical Center, Washington, DC.
24
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR.
25
Department of Pediatrics, Georgetown University, Washington, DC.
26
Department of Oncology, Georgetown University, Washington, DC.
27
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.
28
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
29
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN.
30
Department of Statistics, Children's Oncology Group, Monrovia, CA.
31
Keck School of Medicine, University of Southern California, Los Angeles, CA.
32
Harvard Medical School, Boston, MA.
33
Department of Pathology and Cancer Center, Massachusetts General Hospital, Boston, MA.
34
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.
35
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
36
Division of Hematology/Oncology, Boston Children's Hospital and Harvard Medical School, Boston, MA.
37
Department of Pediatrics, Benioff Children's Hospital, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
#
Contributed equally

Erratum in

Abstract

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 or CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and could therefore be candidates for experimental therapies. In addition, few molecular pathways aside from the RAS-MAPK pathway have been identified that could serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia to expand knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, splicing, Polycomb repressive complex 2 (PRC2) and transcription. Notably, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome.

PMID:
26457647
PMCID:
PMC4626387
DOI:
10.1038/ng.3400
[Indexed for MEDLINE]
Free PMC Article

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