title: Targeted next-generation sequencing of dedifferentiated chondrosarcoma in the skull base reveals combined TP53 and PTEN mutations with increased proliferation index, an implication for pathogenesis.
abstract: Dedifferentiated chondrosarcoma (DDCS) is a rare disease with a dismal prognosis. DDCS consists of two morphologically distinct components: the cartilaginous and noncartilaginous components. Whether the two components originate from the same progenitor cells has been controversial. Recurrent DDCS commonly displays increased proliferation compared with the primary tumor. However, there is no conclusive explanation for this mechanism. In this paper, we present two DDCSs in the sellar region. Patient 1 exclusively exhibited a noncartilaginous component with a TP53 frameshift mutation in the pathological specimens from the first surgery. The tumor recurred after radiation therapy with an exceedingly increased proliferation index. Targeted next-generation sequencing (NGS) revealed the presence of both a TP53 mutation and a PTEN deletion in the cartilaginous and the noncartilaginous components of the recurrent tumor. Fluorescence in situ hybridization and immunostaining confirmed reduced DNA copy number and protein levels of the PTEN gene as a result of the PTEN deletion. Patient 2 exhibited both cartilaginous and noncartilaginous components in the surgical specimens. Targeted NGS of cells from both components showed neither TP53 nor PTEN mutations, making Patient 2 a naïve TP53 and PTEN control for comparison. In conclusion, additional PTEN loss in the background of the TP53 mutation could be the cause of increased proliferation capacity in the recurrent tumor.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiafei
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cao
authors.affiliation: Binhai Genomics Institute, BGI-Tianjin, Tianjin, China.|Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin, China.|Department of Cancer Research, Jingke Biotech, Guangzhou, China.
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: DeLaney
authors.affiliation: Institute for Mathematical Sciences, Renmin University of China, Beijing, China.
authors.forename: Xinqi
authors.initials: X
authors.lastname: Gong
authors.affiliation: Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jianjiao
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Binhai Genomics Institute, BGI-Tianjin, Tianjin, China.|Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Binhai Genomics Institute, BGI-Tianjin, Tianjin, China.|Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin, China.
authors.forename: Pangzehuan
authors.initials: P
authors.lastname: Tian
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xing
mesh_terms: D000328:Adult; D054337:Cell Dedifferentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics* / Q000528:radiation effects; D002813:Chondrosarcoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000532:radiotherapy; D016368:Frameshift Mutation; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008297:Male; D008940:Mitotic Index; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D035583:Rare Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000532:radiotherapy; D019291:Skull Base / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PTEN; TP53; chondrosarcoma; dedifferentiated; proliferation