title: Compound HRAS/PIK3CA mutations in Chinese patients with alveolar rhabdomyosarcomas.
abstract: The rhabdomyosarcoma (RMS) is the most common type of soft tissue tumor in children and adolescents; yet only a few screens for oncogenic mutations have been conducted for RMS. To identify novel mutations and potential therapeutic targets, we conducted a high-throughput Sequenom mass spectrometry-based analysis of 238 known mutations in 19 oncogenes in 17 primary formalin-fixed paraffin-embedded RMS tissue samples and two RMS cell lines. Mutations were detected in 31.6% (6 of 19) of the RMS specimens. Specifically, mutations in the NRAS gene were found in 27.3% (3 of 11) of embryonal RMS cases, while mutations in NRAS, HRAS, and PIK3CA genes were identified in 37.5% (3 of 8) of alveolar RMS (ARMS) cases; moreover, PIK3CA mutations were found in 25% (2 of 8) of ARMS specimens. The results demonstrate that tumor profiling in archival tissue samples is a useful tool for identifying diagnostic markers and potential therapeutic targets and suggests that these HRAS/ PIK3CA mutations play a critical role in the genesis of RMS.
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, China E-mail : lifeng7855@126.com.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Liu
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Li
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Li
authors.forename: Yun-Zhao
authors.initials: YZ
authors.lastname: Chen
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Cui
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Hu
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D002681:China; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D059645:Mutation Rate; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000401:mortality*; D017422:Sequence Analysis, DNA; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)