Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma

• DOI: 10.1016/j.celrep.2014.03.003
• Publication Date: 2014-04-03T17:30:51Z
• Authors: 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
• Keywords: Pediatric cancer

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