Clinical and molecular features of sacrum chordoma in Chinese patients

Zonghan Xu; Ling Zhang; Lijun Wen; Hongying Chao; Qinrong Wang; Miao Sun; Hongjie Shen; Suning Chen; Zheng Wang; Jian Lu

doi:10.21037/atm-21-6617

Clinical and molecular features of sacrum chordoma in Chinese patients

Ann Transl Med. 2022 Jan;10(2):61. doi: 10.21037/atm-21-6617.

Authors

Zonghan Xu^#¹, Ling Zhang^#², Lijun Wen^#^{2

3}, Hongying Chao⁴, Qinrong Wang², Miao Sun⁵, Hongjie Shen², Suning Chen^{2

3}, Zheng Wang^#^{2

6}, Jian Lu^#¹

Affiliations

¹ Department of Orthopedics, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
² National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
³ Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
⁴ Department of Hematology, Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou, China.
⁵ Department of Hematology, Jingjiang People's Hospital, Jingjiang, China.
⁶ Suzhou Jsuniwell Medical Laboratory, Suzhou, China.

^# Contributed equally.

Abstract

Background: 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.

Methods: 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.

Results: The driver genes Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA), Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), and Phosphatase And Tensin Homolog (PTEN) 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 (CLDN9) may play a critical role in the development and progression of sacrum chordoma.

Conclusions: 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.

Keywords: Chordoma; PI3K/mTOR signaling pathway; recombinant CLDN9; whole-exome-sequencing (WES).