The genomic landscape of pediatric acute lymphoblastic leukemia.

Autor: Brady SW; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Roberts KG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Gu Z; Department of Computational and Quantitative Medicine & Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA., Shi L; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Pounds S; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Pei D; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Cheng C; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Dai Y; Department of Biostatistics, University of Florida, Gainesville, FL, USA., Devidas M; Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA., Qu C; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Hill AN; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Payne-Turner D; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Ma X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Iacobucci I; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Baviskar P; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Wei L; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Arunachalam S; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Hagiwara K; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Liu Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Flasch DA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Liu Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Parker M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Chen X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Elsayed AH; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA., Pathak O; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Li Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Fan Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Michael JR; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Rusch M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Wilkinson MR; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Foy S; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Hedges DJ; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Newman S; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Zhou X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Wang J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Reilly C; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Sioson E; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Rice SV; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Pastor Loyola V; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA., Wu G; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA., Rampersaud E; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA., Reshmi SC; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Gastier-Foster J; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Guidry Auvil JM; Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.; Office of Data Sharing, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Gesuwan P; Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Smith MA; Cancer Therapeutics Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Winick N; Department of Pediatric Hematology Oncology and Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Carroll AJ; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA., Heerema NA; The Ohio State University, Columbus, OH, USA., Harvey RC; Department of Pathology, University of New Mexico Cancer Center, Albuquerque, NM, USA., Willman CL; Mayo Clinical Comprehensive Cancer Center, Rochester, MN, USA., Larsen E; Department of Pediatrics, Maine Children's Cancer Program, Scarborough, ME, USA., Raetz EA; Department of Pediatrics and Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA., Borowitz MJ; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA., Wood BL; Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA., Carroll WL; Department of Pediatrics and Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA., Zweidler-McKay PA; ImmunoGen, Inc., Waltham, MA, USA., Rabin KR; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Mattano LA; HARP Pharma Consulting, Mystic, CT, USA., Maloney KW; Department of Pediatrics and Children's Hospital Colorado, University of Colorado, Aurora, CO, USA., Winter SS; Children's Minnesota Research Institute and Cancer and Blood Disorders Program, Minneapolis, MN, USA., Burke MJ; Division of Pediatric Hematology-Oncology, Medical College of Wisconsin, Milwaukee, WI, USA., Salzer W; Uniformed Services University, School of Medicine, Bethesda, MD, USA., Dunsmore KP; Department of Pediatrics, University of Virginia, Charlottesville, VA, USA., Angiolillo AL; Children's National Medical Center, Washington, DC, USA., Crews KR; Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA., Downing JR; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA., Jeha S; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Pui CH; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Evans WE; Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA., Yang JJ; Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA., Relling MV; Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA., Gerhard DS; Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Loh ML; Department of Pediatrics, Benioff Children's Hospital and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Hunger SP; Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Hungers@chop.edu., Zhang J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. jinghui.zhang@stjude.org., Mullighan CG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. charles.mullighan@stjude.org.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2022 Sep; Vol. 54 (9), pp. 1376-1389. Date of Electronic Publication: 2022 Sep 01.
DOI: 10.1038/s41588-022-01159-z
Abstrakt: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal gains in B-ALL cases with intrachromosomal amplification of chromosome 21. We also demonstrate the prognostic significance of genetic alterations within subtypes. Intriguingly, DUX4- and KMT2A-rearranged subtypes separate into CEBPA/FLT3- or NFATC4-expressing subgroups with potential clinical implications. Together, these results deepen understanding of the ALL genomic landscape and associated outcomes.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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