Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors

Jack F. Shern, Li Chen, Juliann Chmielecki, Jun S. Wei, Rajesh Patidar, Mara Rosenberg, Lauren Ambrogio, Daniel Auclair, Jianjun Wang, Young K. Song, Catherine Tolman, Laura Hurd, Hongling Liao, Shile Zhang, Dominik Bogen, Andrew S. Brohl, Sivasish Sindiri, Daniel Catchpoole, Thomas Badgett, Gad GetzJaume Mora, James R. Anderson, Stephen X. Skapek, Frederic G. Barr, Matthew Meyerson, Douglas S. Hawkins, Javed Khan

Research output: Contribution to journalArticle

263 Scopus citations


Despite gains in survival, outcomes for patients with metastatic or recurrent rhabdomyosarcoma remain dismal. In a collaboration between the National Cancer Institute, Children's Oncology Group, and Broad Institute, we performed whole-genome, whole-exome, and transcriptome sequencing to characterize the landscape of somatic alterations in 147 tumor/ normal pairs. Two genotypes are evident in rhabdomyosarcoma tumors: those characterized by the PAX3 or PAX7 fusion and those that lack these fusions but harbor mutations in key signaling pathways. The overall burden of somatic mutations in rhabdomyosarcoma is relatively low, especially in tumors that harbor a PAX3/7 gene fusion. In addition to previously reported mutations in NRAS, KRAS, HRAS, FGFR4, PIK3CA, and CTNNB1, we found novel recurrent mutations in FBXW7 and BCOR, providing potential new avenues for therapeutic intervention. Furthermore, alteration of the receptor tyrosine kinase/ RAS / PIK3CA axis affects 93% of cases, providing a framework for genomics-directed therapies that might improve outcomes for patients with rhabdomyosarcoma.

Original languageEnglish (US)
Pages (from-to)216-231
Number of pages16
JournalCancer Discovery
Issue number2
Publication statusPublished - Feb 2014


ASJC Scopus subject areas

  • Oncology

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