Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma

被引：625

作者：

Chen, Xiang ^{[1
]}

Bahrami, Armita ^{[2
]}

Pappo, Alberto ^{[3
]}

Easton, John ^{[1
]}

Dalton, James ^{[2
]}

Hedlund, Erin ^{[1
]}

Ellison, David ^{[2
]}

Shurtleff, Sheila ^{[2
]}

Wu, Gang ^{[1
]}

Wei, Lei ^{[1
]}

Parker, Matthew ^{[1
]}

Rusch, Michael ^{[1
]}

Nagahawatte, Panduka ^{[1
]}

Wu, Jianrong ^{[4
]}

Mao, Shenghua ^{[4
]}

Boggs, Kristy ^{[1
]}

Mulder, Heather ^{[1
]}

Yergeau, Donald ^{[1
]}

Lu, Charles ^{[6
]}

Ding, Li ^{[6
]}

Edmonson, Michael ^{[1
]}

Qu, Chunxu ^{[1
]}

Wang, Jianmin ^{[1
]}

Li, Yongjin ^{[1
]}

Navid, Fariba ^{[3
]}

Daw, Najat C. ^{[5
]}

Mardis, Elaine R. ^{[6
,7
,8
]}

Wilson, Richard K. ^{[6
,7
,9
]}

Downing, James R. ^{[3
]}

Zhang, Jinghui ^{[1
]}

Dyer, Michael A. ^{[10
,11
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[3] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[4] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA

[5] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[6] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA

[7] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA

[8] Washington Univ, Sch Med, Dept Med, St Louis, MO 63108 USA

[9] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63108 USA

[10] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

[11] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

CELL REPORTS | 2014年 / 7卷 / 01期

关键词：

CLINICOPATHOLOGICAL FEATURES; PROSTATE-CANCER; MUTATIONS; P53; GENOMES;

D O I：

10.1016/j.celrep.2014.03.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：104 / 112

页数：9

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