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. 2023 Jan 4;29(1):261-270.
doi: 10.1158/1078-0432.CCR-22-1865.

Gene Expression Profiling Identifies Two Chordoma Subtypes Associated with Distinct Molecular Mechanisms and Clinical Outcomes

Jiwei Bai  1   2   3 , Jianxin Shi  4 , Yazhuo Zhang  1   2   3   5 , Chuzhong Li  1   2   3   5 , Yujia Xiong  1 , Hela Koka  4 , Difei Wang  4   6 , Tongwu Zhang  4 , Lei Song  4   6 , Wen Luo  4   6 , Bin Zhu  4   6 , Belynda Hicks  4   6 , Amy Hutchinson  4   6 , Erin Kirk  7 , Melissa A Troester  7 , Mingxuan Li  1 , Yutao Shen  1 , Tianshun Ma  1 , Junmei Wang  1   3   5 , Xing Liu  1   3   5 , Shuai Wang  1 , Songbai Gui  2   3 , Mary L McMaster  4 , Stephen J Chanock  4 , Dilys M Parry  4 , Alisa M Goldstein  4 , Xiaohong R Yang  4
Affiliations

Gene Expression Profiling Identifies Two Chordoma Subtypes Associated with Distinct Molecular Mechanisms and Clinical Outcomes

Jiwei Bai et al. Clin Cancer Res. .

Abstract

Purpose: Chordoma is a rare bone tumor with a high recurrence rate and limited treatment options. The aim of this study was to identify molecular subtypes of chordoma that may improve clinical management.

Experimental design: We conducted RNA sequencing in 48 tumors from patients with Chinese skull-base chordoma and identified two major molecular subtypes. We then replicated the classification using a NanoString panel in 48 patients with chordoma from North America.

Results: Tumors in one subtype were more likely to have somatic mutations and reduced expression in chromatin remodeling genes, such as PBRM1 and SETD2, whereas the other subtype was characterized by the upregulation of genes in epithelial-mesenchymal transition and Sonic Hedgehog pathways. IHC staining of top differentially expressed genes between the two subtypes in 312 patients with Chinese chordoma with long-term follow-up data showed that the expression of some markers such as PTCH1 was significantly associated with survival outcomes.

Conclusions: Our findings may improve the understanding of subtype-specific tumorigenesis of chordoma and inform clinical prognostication and targeted options.

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Conflict of interest statement

Conflict of Interest: The authors declare no conflict of interests.

Figures

Figure 1.
Figure 1.
Unsupervised consensus clustering of tumors based on RNASeq data from 48 Chinese skull-base chordoma patients
Figure 1.
Figure 1.
Unsupervised consensus clustering of tumors based on RNASeq data from 48 Chinese skull-base chordoma patients
Figure 1.
Figure 1.
Unsupervised consensus clustering of tumors based on RNASeq data from 48 Chinese skull-base chordoma patients
Figure 2.
Figure 2.
Differentially expressed genes between CC1 and CC2
Figure 2.
Figure 2.
Differentially expressed genes between CC1 and CC2
Figure 3.
Figure 3.
Gene expression profiling based on the NanoString panel in chordoma patients from North America
Figure 4.
Figure 4.
Expression of PTCH1 in relation to overall survival (upper panel) and recurrence-free survival (lower panel) in 312 Chinese chordoma patients with long-term follow-up data
See this image and copyright information in PMC

References

    1. Salisbury JR, Deverell MH, Cookson MJ, Whimster WF. Three-dimensional reconstruction of human embryonic notochords: clue to the pathogenesis of chordoma. J Pathol 1993;171(1):59–62 doi 10.1002/path.1711710112. - DOI - PubMed
    1. Boriani S, Bandiera S, Biagini R, Bacchini P, Boriani L, Cappuccio M, et al. Chordoma of the mobile spine: fifty years of experience. Spine (Phila Pa 1976) 2006;31(4):493–503 doi 10.1097/01.brs.0000200038.30869.27. - DOI - PubMed
    1. Zuckerman SL, Bilsky MH, Laufer I. Chordomas of the Skull Base, Mobile Spine, and Sacrum: An Epidemiologic Investigation of Presentation, Treatment, and Survival. World Neurosurg 2018;113:e618–e27 doi 10.1016/j.wneu.2018.02.109. - DOI - PubMed
    1. Parry DM, McMaster ML, Liebsch NJ, Patronas NJ, Quezado MM, Zametkin D, et al. Clinical findings in families with chordoma with and without T gene duplications and in patients with sporadic chordoma reported to the Surveillance, Epidemiology, and End Results program. J Neurosurg 2020:1–10 doi 10.3171/2020.4.JNS193505. - DOI - PMC - PubMed
    1. Mercado CE, Holtzman AL, Rotondo R, Rutenberg MS, Mendenhall WM. Proton therapy for skull base tumors: A review of clinical outcomes for chordomas and chondrosarcomas. Head Neck 2019;41(2):536–41 doi 10.1002/hed.25479. - DOI - PubMed

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