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Published on: April 12, 2019
Clinical and molecular features of sacrum chordoma in Chinese patients
Zonghan Xu1, Ling Zhang2, Lijun Wen2,3
1Department of Orthopedics, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
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.
Insights
This study identifies key genes like PIK3CA and CLDN9 in sacrum chordoma, offering potential new therapeutic targets for this rare bone cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Chordoma is a rare, aggressive bone tumor with poor prognosis.
- The underlying genetic mutations driving chordoma remain largely unknown.
- Understanding chordoma's molecular pathogenesis is crucial for developing effective therapies.
Purpose of the Study:
- To identify driver genes and signaling pathways involved in sacrum chordoma.
- To explore potential molecular therapeutic targets for chordoma.
- To elucidate the genetic landscape of chordoma in Chinese patients.
Main Methods:
- Whole-exome sequencing (WES) of 8 sacrum chordoma tissues and matched blood samples.
- Bioinformatic analysis including mutation identification, pathway enrichment, and identification of significantly mutated genes (SMGs).
- Validation of key genes using immunohistochemistry, Sanger sequencing, and GeneChip analysis.
Main Results:
- Identified Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA), Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), and Phosphatase And Tensin Homolog (PTEN) as driver genes.
- These genes are enriched in the Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, indicating potential therapeutic targets.
- Claudin 9 (CLDN9) was identified as a significantly mutated gene potentially critical for chordoma development.
Conclusions:
- The study reveals the genetic signature of sacrum chordoma.
- Identified PIK3CA, PIK3R1, PTEN, and CLDN9 as key genes in chordoma pathogenesis.
- Findings provide a basis for developing novel molecular targeted therapies for sacrum chordoma.
