TY  - JOUR
A1  - Totoki, Yasushi
A1  - Yoshida, Akihiko
A1  - Hosoda, Fumie
A1  - Nakamura, Hiromi
A1  - Hama, Natsuko
A1  - Ogura, Koichi
A1  - Yoshida, Aki
A1  - Fujiwara, Tomohiro
A1  - Arai, Yasuhito
A1  - Toguchida, Junya
A1  - Tsuda, Hitoshi
A1  - Miyano, Satoru
A1  - Kawai, Akira
A1  - Shibata, Tatsuhiro
T1  - Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma
Y1  - 2014/09/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1411 
EP  - 1420 
DO  - 10.1101/gr.160598.113 
VL  - 24 
IS  - 9 
UR  - http://genome.cshlp.org/content/24/9/1411.abstract 
N2  - Chondrosarcoma is the second most frequent malignant bone tumor. However, the etiological background of chondrosarcomagenesis remains largely unknown, along with details on molecular alterations and potential therapeutic targets. Massively parallel paired-end sequencing of whole genomes of 10 primary chondrosarcomas revealed that the process of accumulation of somatic mutations is homogeneous irrespective of the pathological subtype or the presence of IDH1 mutations, is unique among a range of cancer types, and shares significant commonalities with that of prostate cancer. Clusters of structural alterations localized within a single chromosome were observed in four cases. Combined with targeted resequencing of additional cartilaginous tumor cohorts, we identified somatic alterations of the COL2A1 gene, which encodes an essential extracellular matrix protein in chondroskeletal development, in 19.3% of chondrosarcoma and 31.7% of enchondroma cases. Epigenetic regulators (IDH1 and YEATS2) and an activin/BMP signal component (ACVR2A) were recurrently altered. Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases. With the characteristic accumulative process of somatic changes as a background, molecular defects in chondrogenesis and aberrant epigenetic control are primarily causative of both benign and malignant cartilaginous tumors. 
ER  -