Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma

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 sa...

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Published in:Cell reports (Cambridge) Vol. 7; no. 1; pp. 104 - 112
Main Authors: Chen, Xiang, Bahrami, Armita, Pappo, Alberto, Easton, John, Dalton, James, Hedlund, Erin, Ellison, David, Shurtleff, Sheila, Wu, Gang, Wei, Lei, Parker, Matthew, Rusch, Michael, Nagahawatte, Panduka, Wu, Jianrong, Mao, Shenghua, Boggs, Kristy, Mulder, Heather, Yergeau, Donald, Lu, Charles, Ding, Li, Edmonson, Michael, Qu, Chunxu, Wang, Jianmin, Li, Yongjin, Navid, Fariba, Daw, Najat C., Mardis, Elaine R., Wilson, Richard K., Downing, James R., Zhang, Jinghui, Dyer, Michael A.
Format: Journal Article
Language:English
Published: United States Elsevier 01.04.2014
Subjects:
Adolescent
Bone Neoplasms - genetics
Bone Neoplasms - pathology
Carcinogenesis - genetics
Carcinogenesis - pathology
Child
Child, Preschool
Disease Progression
DNA Copy Number Variations
DNA, Neoplasm - genetics
Genome, Human
Humans
Mutation
Neoplasm Metastasis
Osteosarcoma - genetics
Osteosarcoma - pathology
Polymorphism, Single Nucleotide
ISSN:2211-1247, 2211-1247
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Summary: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.
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These authors contributed equally to the work.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2014.03.003