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Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations

Bousquet, Marina and Noirot, Céline and Accadbled, Franck and Sales de Gauzy, Jérôme and Castex, Marie-Pierre and Brousset, Pierre and Gomez-Brouchet, Anne Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations. (2016) Annals of Oncology, 27 (4). 738-744. ISSN 0923-7534

(Document in English)

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Official URL: https://doi.org/10.1093/annonc/mdw009


BACKGROUND: Whole-genome sequencing studies have recently shown that osteosarcomas (OSs) display high rates of structural variation, i.e. they contain many somatic mutations and copy number alterations. TP53 and RB1 show recurrent somatic alterations in concordant studies, suggesting that they could be key players in bone oncogenesis. PATIENTS AND METHODS: we carried out whole-genome sequencing of DNA from seven high-grade OS samples matched with normal tissue from the same patients. RESULTS: We confirmed the presence of genetic alterations of the TP53 (including novel unreported mutations) and RB1 genes. Most interestingly, we identified a total of 84 point mutations and 4 deletions related to 82 different genes in OS samples, of which only 15 have been previously reported. Interestingly, the number of mutated genes (ranging from 4 to 8) was lower in TP53mut cases compared with TP53wt cases (ranging from 14 to 45). This was also true for the mutated RB1 case. We also observed that a dedifferentiated OS harboring MDM2 amplification did not carry any other mutations. CONCLUSION: This study suggests that bone oncogenesis driven by TP53 or RB1 mutations occurs on a background of relative genetic stability and that the dedifferentiated OS subtype represents a clinico-pathological entity with distinct oncogenic mechanisms and thus requires different therapeutic management

Item Type:Article
Additional Information:Thanks to Oxford University Press. The definitive version is available at https://academic.oup.com/ The original PDF of the article can be found at https://academic.oup.com/annonc/article/27/4/738/2769770/Whole-exome-sequencing-in-osteosarcoma-reveals
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
French research institutions > Institut National de la Recherche Agronomique - INRA (FRANCE)
French research institutions > Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE)
Other partners > Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE)
Deposited On:23 Oct 2017 09:34

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