TY  - JOUR
A1  - Kovac, Michal
A1  - Blattmann, Claudia
A1  - Ribi, Sebastian
A1  - Smida, Jan
A1  - Müller, Nikola S.
A1  - Engert, Florian
A1  - Castro-Giner, Francesc
A1  - Weischenfeldt, Joachim
A1  - Kovacova, Monika
A1  - Krieg, Andreas
A1  - Andreou, Dimosthenis
A1  - Tunn, Per-Ulf
A1  - Dürr, Hans Roland
A1  - Rechl, Hans
A1  - Schaser, Klaus-Dieter
A1  - Melcher, Ingo
A1  - Burdach, Stefan
A1  - Kulozik, Andreas
A1  - Specht, Katja
A1  - Heinimann, Karl
A1  - Fulda, Simone
A1  - Bielack, Stefan S.
A1  - Jundt, Gernot
A1  - Tomlinson, Ian
A1  - Korbel, Jan Oliver
A1  - Nathrath, Michaela
A1  - Baumhoer, Daniel
T1  - Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency
T2  - Nature Communications
N2  - Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours. We identify 14 genes as the main drivers, of which some were formerly unknown in the context of osteosarcoma. None of the drivers is clearly responsible for the majority of tumours and even TP53 mutations are frequently mapped into subclones. However, >80% of osteosarcomas exhibit a specific combination of single-base substitutions, LOH, or large-scale genome instability signatures characteristic of BRCA1/2-deficient tumours. Our findings imply that multiple oncogenic pathways drive chromosomal instability during osteosarcoma evolution and result in the acquisition of BRCA-like traits, which could be therapeutically exploited.
KW  - Bone cancer
KW  - Cancer genetics
KW  - DNA sequencing
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50605
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-506058
SN  - 2041-1723
N1  - This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
VL  - 6
IS  - Art. 8940
SP  - 1
EP  - 9
PB  - Nature Publishing Group UK
CY  - [London]
ER  -