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.
Keywords: chordoma, PTEN, CDKN2A, gene sequencing, fluorescence in situ hybridization, prognosis