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

doi:10.1016/j.celrep.2014.03.003

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

Internal Medicine

Research output: Contribution to journal › Article › peer-review

646 Scopus citations

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.

Original language	English
Pages (from-to)	104-112
Number of pages	9
Journal	Cell Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2014.03.003
State	Published - 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.

Funding

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.

Funders	Funder number
Markey Cancer Center's Cancer Center Support	CA21765
St. Jude Children's Research Hospital -Washington University
National Institutes of Health (NIH)	EY018599, CA168875
National Institutes of Health (NIH)
National Eye Institute/National Institutes of Health	R01EY014867
National Eye Institute/National Institutes of Health
National Childhood Cancer Registry – National Cancer Institute
American Lebanese Syrian Associated Charities

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2014.03.003

Cite this

Chen, X., Bahrami, A., Pappo, A., Easton, J., Dalton, J., Hedlund, E., Ellison, D., Shurtleff, S., Wu, G., Wei, L., Parker, M., Rusch, M., Nagahawatte, P., Wu, J., Mao, S., Boggs, K., Mulder, H., Yergeau, D., Lu, C., ... Dyer, M. A. (2014). Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Reports, 7(1), 104-112. https://doi.org/10.1016/j.celrep.2014.03.003

@article{2871f280e46241f184d8b5a084af0e9b,

title = "Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma",

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.",

author = "Xiang Chen and Armita Bahrami and Alberto Pappo and John Easton and James Dalton and Erin Hedlund and David Ellison and Sheila Shurtleff and Gang Wu and Lei Wei and Matthew Parker and Michael Rusch and Panduka Nagahawatte and Jianrong Wu and Shenghua Mao and Kristy Boggs and Heather Mulder and Donald Yergeau and Charles Lu and Li Ding and Michael Edmonson and Chunxu Qu and Jianmin Wang and Yongjin Li and Fariba Navid and Daw, \{Najat C.\} and Mardis, \{Elaine R.\} and Wilson, \{Richard K.\} and Downing, \{James R.\} and Jinghui Zhang and Dyer, \{Michael A.\}",

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. ",

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doi = "10.1016/j.celrep.2014.03.003",

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Chen, X, Bahrami, A, Pappo, A, Easton, J, Dalton, J, Hedlund, E, Ellison, D, Shurtleff, S, Wu, G, Wei, L, Parker, M, Rusch, M, Nagahawatte, P, Wu, J, Mao, S, Boggs, K, Mulder, H, Yergeau, D, Lu, C, Ding, L, Edmonson, M, Qu, C, Wang, J, Li, Y, Navid, F, Daw, NC, Mardis, ER, Wilson, RK, Downing, JR, Zhang, J & Dyer, MA 2014, 'Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma', Cell Reports, vol. 7, no. 1, pp. 104-112. https://doi.org/10.1016/j.celrep.2014.03.003

TY - JOUR

T1 - Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma

AU - Chen, Xiang

AU - Bahrami, Armita

AU - Pappo, Alberto

AU - Easton, John

AU - Dalton, James

AU - Hedlund, Erin

AU - Ellison, David

AU - Shurtleff, Sheila

AU - Wu, Gang

AU - Wei, Lei

AU - Parker, Matthew

AU - Rusch, Michael

AU - Nagahawatte, Panduka

AU - Wu, Jianrong

AU - Mao, Shenghua

AU - Boggs, Kristy

AU - Mulder, Heather

AU - Yergeau, Donald

AU - Lu, Charles

AU - Ding, Li

AU - Edmonson, Michael

AU - Qu, Chunxu

AU - Wang, Jianmin

AU - Li, Yongjin

AU - Navid, Fariba

AU - Daw, Najat C.

AU - Mardis, Elaine R.

AU - Wilson, Richard K.

AU - Downing, James R.

AU - Zhang, Jinghui

AU - Dyer, Michael A.

N1 - 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.

PY - 2014/10/4

Y1 - 2014/10/4

N2 - 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.

AB - 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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UR - https://www.scopus.com/pages/publications/84898027965#tab=citedBy

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DO - 10.1016/j.celrep.2014.03.003

M3 - Article

C2 - 24703847

AN - SCOPUS:84898027965

SN - 2211-1247

VL - 7

SP - 104

EP - 112

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

Access to Document

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