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Cell Rep. 2014 Apr 10;7(1):104-12. doi: 10.1016/j.celrep.2014.03.003. Epub 2014 Apr 3.

Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma.

Author information

1
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
3
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
5
The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
6
University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
7
The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
8
The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
9
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: jinghui.zhang@stjude.org.
10
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: michael.dyer@stjude.org.

Abstract

Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs) and copy number alterations (CNAs). To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs) exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%-53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods.

PMID:
24703847
PMCID:
PMC4096827
DOI:
10.1016/j.celrep.2014.03.003
[Indexed for MEDLINE]
Free PMC Article

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