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

常规和软骨样脊索瘤中 PTEN 和 CDKN2A 肿瘤抑制基因的缺乏: 分子特征和临床相关性。

  • 影响因子:2.97
  • DOI:10.2147/OTT.S252990
  • 作者列表:"Yang C","Sun J","Yong L","Liang C","Liu T","Xu Y","Yang J","Liu X
  • 发表时间:2020-05-25
Abstract

Introduction: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.

摘要

导读: 脊索瘤是一种主要累及颅底和脊柱的恶性肿瘤。本研究旨在探讨 PTEN 和 CDKN2A 在常规和软骨样脊索瘤中的分子特征及其与临床预后的相关性。 材料与方法: 共纳入 42 例患者,其中常规脊索瘤 26 例,软骨样脊索瘤 16 例。收集临床病理特征和组织标本。进行基因测序和荧光原位杂交,鉴定 PTEN 和 CDKN2A 基因的遗传改变。采用免疫组织化学染色半定量评价 PTEN 和 CDKN2A 的表达。 结果: 基因测序发现一个内含子 SNP (c.80-96A>G) 和一个错义突变 (c.10G> a; p。gly4Arg) 在 PTEN 基因和一个错义突变 (c.442G> a; p.CDKN2A 基因中的 Ala148Thr)。25 例 (59.5%) 发现 PTEN 位点缺失,28 例 (66.7%) 发现 CDKN2A 位点缺失。无进展生存期 (PFS)/总生存期 (OS) 与 PTEN 或 CDKN2A 缺失之间无显著相关性。PTEN 低表达的患者 PFS 和 OS 明显短于高表达的患者,而 CDKN2A 低表达患者与 CDKN2A 高表达患者的 PFS 或 OS 无显著差异。 结论: 我们的研究结果描绘了脊索瘤中 PTEN 和 CDKN2A 的遗传景观和表达。PTEN 表达可能作为脊索瘤的预后和预测生物标志物。

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作者列表:["Yang D","Liu K","Fan L","Liang W","Xu T","Jiang W","Lu H","Jiang J","Wang C","Li G","Zhang X"]

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影响因子:11.08
发表时间:2020-01-13
DOI:10.1200/JCO.19.00827
作者列表:["Kelley LM","Schlegel M","Hecker-Nolting S","Kevric M","Haller B","Rössig C","Reichardt P","Kager L","Kühne T","Gosheger G","Windhager R","Specht K","Rechl H","Tunn PU","Baumhoer D","Wirth T","Werner M","von Kalle T","Nathrath M","Burdach S","Bielack S","von Lüttichau I"]

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