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 DingMichael 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

Research output: Contribution to journalArticlepeer-review

411 Scopus citations


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.

Original languageEnglish
Pages (from-to)104-112
Number of pages9
JournalCell Reports
Issue number1
StatePublished - Oct 4 2014

Bibliographical note

Funding Information:
This work was supported, in part, by Cancer Center Support (CA21765) from the NCI, grants to M.A.D from the NIH (EY014867, EY018599, and CA168875), and the American Lebanese Syrian Associated Charities (ALSAC). M.A.D. is an HHMI Investigator. The whole-genome sequencing was supported as part of the St. Jude Children's Research Hospital -Washington University Pediatric Cancer Genome Project.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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