title: Oncogene mutation profiling reveals poor prognosis associated with FGFR1/3 mutation in liposarcoma.
abstract: Liposarcoma (LPS) is one of the most prevalent soft tissue sarcomas. LPS shows a poor response to radiation and chemotherapy. The causes of death in patients with LPS include locally recurrent and metastatic disease. We sought to examine novel gene mutations and pathways in primary and matched recurrent LPSs to identify potential therapeutic targets. We conducted a high-throughput analysis of 238 known mutations in 19 oncogenes using Sequenom MassARRAY technology. Nucleic acids were extracted from 19 primary and recurrent LPS samples, encompassing 9 dedifferentiated LPSs (DDLPS), 9 myxoid/round cell LPSs, and 1 pleomorphic LPS. Mutation screening revealed missense mutations in 21.1% (4/19) of the LPS specimens, including 4 different genes (FGFR1, FGFR3, PIK3CA, and KIT). Based on histologic subtypes, 22.2% DDLPS (2/9) and 22.2% myxoid cell LPS (2/9) contained gene mutations. Specifically, 3 (23.1%) of 13 primary tumors harbored mutations. Furthermore, although gene mutations were identified in 1 (11.1%) of 9 recurrent LPS samples, the difference between the primary and the recurrence was not statistically significant. Analysis of patient survival data indicated that patients harboring FGFR1/3 mutations experienced reduced overall survival (P<.05). Despite the limited number of samples, our findings provide the first evidence of FGFR1/3 mutations in DDLPS, which were associated with poor clinical outcomes. The FGFR pathway may play an important role in the development and progression of DDLPS and warrants further investigation; moreover, PIK3CA mutation is a common event (11.1%) in myxoid cell LPS.
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China; Department of Pathology, The Affiliated Hospital of Zun Yi Medical College, Zunyi, Guizhou 563000, China.
authors.forename: Chengfang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China.
authors.forename: Yaoyuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China. Electronic address: liuliu2239@sina.com.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China; Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China. Electronic address: lifeng7855@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002454:Cell Differentiation; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008080:Liposarcoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020125:Mutation, Missense; D009364:Neoplasm Recurrence, Local; D009857:Oncogenes; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C496348:FGFR1 protein, human; C496365:FGFR3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: FGFR1/3; Liposarcomas; MassARRAY technology; Mutations; Oncogenes; Prognosis