Integrative genomic analysis of matched primary and metastatic pediatric osteosarcoma.
Age Factors
Biomarkers, Tumor
/ genetics
Bone Neoplasms
/ genetics
British Columbia
DNA Copy Number Variations
Female
Gene Amplification
Gene Dosage
Genetic Heterogeneity
Genetic Predisposition to Disease
Humans
Male
Microsatellite Instability
Mutation
Neoplasm Recurrence, Local
/ genetics
Osteosarcoma
/ genetics
Phenotype
Polymorphism, Single Nucleotide
Transcriptome
United States
Exome Sequencing
Whole Genome Sequencing
KDR
VEGF
childhood bone sarcomas
genome sequencing
metastasis
osteosarcoma
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
31
12
2018
revised:
23
05
2019
accepted:
20
06
2019
pubmed:
27
6
2019
medline:
14
4
2020
entrez:
26
6
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31236944
doi: 10.1002/path.5319
pmc: PMC9263032
mid: NIHMS1620978
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
319-331Subventions
Organisme : NCI NIH HHS
ID : R44 CA233128
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA257610
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA088199
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014089
Pays : United States
Organisme : NCI NIH HHS
ID : R41 CA203457
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA114757
Pays : United States
Organisme : NCI NIH HHS
ID : RC2 CA148216
Pays : United States
Informations de copyright
© 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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