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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Integrative genomic analysis of matched primary and metastatic pediatric osteosarcoma
Journal of Pathology, Volume 249, No. 3, Year 2019
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Description
Despite being the most common childhood bone tumor, the genomic characterization of osteosarcoma remains incomplete. In particular, very few osteosarcoma metastases have been sequenced to date, critical to better understand mechanisms of progression and evolution in this tumor. We performed an integrated whole genome and exome sequencing analysis of paired primary and metastatic pediatric osteosarcoma specimens to identify recurrent genomic alterations. Sequencing of 13 osteosarcoma patients including 13 primary, 10 metastatic, and 3 locally recurring tumors revealed a highly heterogeneous mutational landscape, including cases of hypermutation and microsatellite instability positivity, but with virtually no recurrent alterations except for mutations involving the tumor suppressor genes RB1 and TP53. At the germline level, we detected alterations in multiple cancer related genes in the majority of the cohort, including those potentially disrupting DNA damage response pathways. Metastases retained only a minimal number of short variants from their corresponding primary tumors, while copy number alterations showed higher conservation. One recurrently amplified gene, KDR, was highly expressed in advanced cases and associated with poor prognosis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors & Co-Authors
Negri, Gian Luca
Canada, Vancouver
British Columbia Cancer Agency
Grande, Bruno M.
Canada, Burnaby
Simon Fraser University
Delaidelli, Alberto
Canada, Vancouver
British Columbia Cancer Agency
Canada, Vancouver
The University of British Columbia
El-Naggar, Amal M.
Canada, Vancouver
British Columbia Cancer Agency
Egypt, Shibin el Kom
Menoufia University Faculty of Medicine
Cochrane, Dawn
Canada, Vancouver
British Columbia Cancer Agency
Lau, Ching C.
United States, Houston
Texas Children's Hospital
Triche, Timothy Junius
United States, Los Angeles
Children's Hospital Los Angeles
United States, Los Angeles
Keck School of Medicine of Usc
Moore, Richard A.
Canada, Vancouver
British Columbia Cancer Agency
Jones, Steven J.M.
Canada, Vancouver
British Columbia Cancer Agency
Montpetit, Alexandre
Canada, Montreal
Centre Universitaire de Santé Mcgill
Marra, Marco A.
Canada, Vancouver
British Columbia Cancer Agency
Canada, Vancouver
The University of British Columbia
Malkin, David
Canada, Toronto
Hospital for Sick Children University of Toronto
Morin, Ryan D.
Canada, Burnaby
Simon Fraser University
Sorensen, Poul H.
Canada, Vancouver
British Columbia Cancer Agency
Canada, Vancouver
The University of British Columbia
Statistics
Citations: 14
Authors: 14
Affiliations: 9
Identifiers
Doi:
10.1002/path.5319
ISSN:
00223417
e-ISSN:
10969896
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health
Study Design
Cohort Study