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
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Lu Gao1,*, Xiafei Hong2,*, Xiaopeng Guo1, Dengfeng Cao3, Xiaohuan Gao4,5,10, Thomas F. DeLaney6, Xinqi Gong7, Rongrong Chen8, Jianjiao Ni9, Yong Yao1, Renzhi Wang1, Xi Chen4,5, Pangzehuan Tian4,5, Bing Xing1
1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
3Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA
4Binhai Genomics Institute, BGI-Tianjin, Tianjin, China
5Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin, China
6Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
7Institute for Mathematical Sciences, Renmin University of China, Beijing, China
8Institute 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
9Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
10Department of Cancer Research, Jingke Biotech, Guangzhou, China
*These authors have contributed equally to this work
Bing Xing, email: firstname.lastname@example.org
Keywords: dedifferentiated, chondrosarcoma, TP53, PTEN, proliferation
Received: November 07, 2015 Accepted: May 08, 2016 Published: May 26, 2016
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.
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