Xu Zonghan, Zhang Ling, Wen Lijun, Chao Hongying, Wang Qinrong, Sun Miao, Shen Hongjie, Chen Suning, Wang Zheng, Lu Jian
Department of Orthopedics, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Ann Transl Med. 2022 Jan;10(2):61. doi: 10.21037/atm-21-6617.
Chordoma is a rare malignant bone tumor with high recurrence and metastasis rates. Little is known about the mutational process of this incurable disease. The aim of our research was to explore the potential driver genes and signal pathways in the pathogenesis of chordoma and provide a new idea for the study of molecular biological therapy of chordoma.
We performed whole-exome-sequencing (WES) on 8 sacrum chordoma tissue samples (matched to peripheral blood samples that had been drawn from patients before surgery) to identify genetic alterations in Chinese patients. We analyzed the sequencing data from known driver genes, pathway enrichment analysis and significantly mutated genes (SMGs) after quality control of sequencing, comparison of reference genomes, analysis of mutations and identification of somatic mutations. Immunohistochemistry staining, Sanger sequencing and GeneChip were used to verify the related genes obtained from the analysis of sequencing data.
The driver genes Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (), Phosphoinositide-3-Kinase Regulatory Subunit 1 (), and Phosphatase And Tensin Homolog () were enriched in the Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway and could be potential therapeutic targets for the treatment of sacrum chordoma. The significantly mutated gene Claudin 9 () may play a critical role in the development and progression of sacrum chordoma.
Collectively, our results identified the genetic signature of sacrum chordoma and could be used to develop a potential promising therapeutic strategy for the treatment of sacrum chordoma in Chinese patients.
脊索瘤是一种罕见的恶性骨肿瘤，复发和转移率高。对于这种无法治愈的疾病的突变过程知之甚少。我们研究的目的是探索脊索瘤发病机制中的潜在驱动基因和信号通路，并为脊索瘤的分子生物学治疗研究提供新思路。
我们对8例骶骨脊索瘤组织样本（与术前采集的患者外周血样本匹配）进行了全外显子测序（WES），以鉴定中国患者的基因改变。在对测序进行质量控制、参考基因组比较、突变分析和体细胞突变鉴定后，我们分析了来自已知驱动基因的测序数据、通路富集分析和显著突变基因（SMGs）。使用免疫组织化学染色、桑格测序和基因芯片来验证从测序数据分析中获得的相关基因。
驱动基因磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（）、磷脂酰肌醇-3-激酶调节亚基1（）和磷酸酶和张力蛋白同源物（）在磷脂酰肌醇3-激酶（PI3K）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路中富集，可能是治疗骶骨脊索瘤的潜在治疗靶点。显著突变基因Claudin 9（）可能在骶骨脊索瘤的发生和发展中起关键作用。
总体而言，我们的结果确定了骶骨脊索瘤的基因特征，可用于为中国患者开发一种潜在的有前景的骶骨脊索瘤治疗策略。
