Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma

Masafumi Seki, Riki Nishimura, Kenichi Yoshida, Teppei Shimamura, Yuichi Shiraishi, Yusuke Sato, Motohiro Kato, Kenichi Chiba, Hiroko Tanaka, Noriko Hoshino, Genta Nagae, Yusuke Shiozawa, Yusuke Okuno, Hajime Hosoi, Yukichi Tanaka, Hajime Okita, Mitsuru Miyachi, Ryota Souzaki, Tomoaki Taguchi, Katsuyoshi KohRyoji Hanada, Keisuke Kato, Yuko Nomura, Masaharu Akiyama, Akira Oka, Takashi Igarashi, Satoru Miyano, Hiroyuki Aburatani, Yasuhide Hayashi, Seishi Ogawa, Junko Takita

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)


Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS.

Original languageEnglish
Article number7557
JournalNature communications
Publication statusPublished - 2015 Jul 3
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy


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