OncoTargets and Therapy (May 2020)

Deficiency of PTEN and CDKN2A Tumor-Suppressor Genes in Conventional and Chondroid Chordomas: Molecular Characteristics and Clinical Relevance

  • Yang C,
  • Sun J,
  • Yong L,
  • Liang C,
  • Liu T,
  • Xu Y,
  • Yang J,
  • Liu X

Journal volume & issue
Vol. Volume 13
pp. 4649 – 4663

Abstract

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Chenlong Yang, 1,* Jianjun Sun, 2,* Lei Yong, 1 Chen Liang, 1 Tie Liu, 3 Yulun Xu, 3 Jun Yang, 2 Xiaoguang Liu 1 1Department of Orthopedics, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Neurosurgery, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 3Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoguang Liu; Jun Yang Email [email protected]; [email protected]: Chordoma is a malignant tumor predominantly involving the skull base and vertebral column. This study aimed to investigate the molecular characteristics of PTEN and CDKN2A in conventional and chondroid chordomas and their correlation with clinical prognosis.Materials and Methods: A total of 42 patients were enrolled, including 26 patients with conventional chordoma and 16 patients with chondroid chordoma. Clinicopathological profiles and tissue specimens were collected. Gene sequencing and fluorescence in situ hybridization were performed to identify genetic alterations in the PTEN and CDKN2A genes. Immunohistochemical staining was used for semiquantitative evaluation of PTEN and CDKN2A expression.Results: Gene sequencing revealed an intron SNP (c.80– 96A>G) and a missense mutation (c.10G>A; p.Gly4Arg) in the PTEN gene and a missense mutation (c.442G>A; p.Ala148Thr) in the CDKN2A gene. Loss of the PTEN locus was identified in 25 (59.5%) cases, and loss of the CDKN2A locus was found in 28 (66.7%) cases. There was no significant correlation between progression-free survival (PFS)/overall survival (OS) and loss of PTEN or CDKN2A. The patients with lower PTEN expression showed significantly shorter PFS and OS than those with higher expression, while there was no significant difference in PFS or OS between patients with lower CDKN2A expression and those with higher CDKN2A expression.Conclusion: Our findings delineated the genetic landscape and expression of PTEN and CDKN2A in chordomas. PTEN expression may serve as a prognostic and predictive biomarker for chordomas.Keywords: chordoma, PTEN, CDKN2A, gene sequencing, fluorescence in situ hybridization, prognosis

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