Cell Reports (Apr 2014)
Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma
- Xiang Chen,
- Armita Bahrami,
- Alberto Pappo,
- John Easton,
- James Dalton,
- Erin Hedlund,
- David Ellison,
- Sheila Shurtleff,
- Gang Wu,
- Lei Wei,
- Matthew Parker,
- Michael Rusch,
- Panduka Nagahawatte,
- Jianrong Wu,
- Shenghua Mao,
- Kristy Boggs,
- Heather Mulder,
- Donald Yergeau,
- Charles Lu,
- Li Ding,
- Michael Edmonson,
- Chunxu Qu,
- Jianmin Wang,
- Yongjin Li,
- Fariba Navid,
- Najat C. Daw,
- Elaine R. Mardis,
- Richard K. Wilson,
- James R. Downing,
- Jinghui Zhang,
- Michael A. Dyer
Affiliations
- Xiang Chen
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Armita Bahrami
- Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Alberto Pappo
- Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- John Easton
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- James Dalton
- Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Erin Hedlund
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- David Ellison
- Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Sheila Shurtleff
- Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Gang Wu
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Lei Wei
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Matthew Parker
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Michael Rusch
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Panduka Nagahawatte
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Jianrong Wu
- Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Shenghua Mao
- Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Kristy Boggs
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Heather Mulder
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Donald Yergeau
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Charles Lu
- The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA
- Li Ding
- The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA
- Michael Edmonson
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Chunxu Qu
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Jianmin Wang
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Yongjin Li
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Fariba Navid
- Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Najat C. Daw
- University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Elaine R. Mardis
- The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA
- Richard K. Wilson
- The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA
- James R. Downing
- Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Jinghui Zhang
- Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Michael A. Dyer
- Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- DOI
- https://doi.org/10.1016/j.celrep.2014.03.003
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 104 – 112
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.
