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Gene Expression Profiling Identifies Two Chordoma Subtypes Associated with Distinct Molecular Mechanisms and Clinical Outcomes.
Bai, Jiwei; Shi, Jianxin; Zhang, Yazhuo; Li, Chuzhong; Xiong, Yujia; Koka, Hela; Wang, Difei; Zhang, Tongwu; Song, Lei; Luo, Wen; Zhu, Bin; Hicks, Belynda; Hutchinson, Amy; Kirk, Erin; Troester, Melissa A; Li, Mingxuan; Shen, Yutao; Ma, Tianshun; Wang, Junmei; Liu, Xing; Wang, Shuai; Gui, Songbai; McMaster, Mary L; Chanock, Stephen J; Parry, Dilys M; Goldstein, Alisa M; Yang, Xiaohong R.
Affiliation
  • Bai J; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
  • Shi J; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • Zhang Y; China National Clinical Research Center for Neurological Diseases, Beijing, China.
  • Li C; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • Xiong Y; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
  • Koka H; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • Wang D; China National Clinical Research Center for Neurological Diseases, Beijing, China.
  • Zhang T; Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, China.
  • Song L; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
  • Luo W; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • Zhu B; China National Clinical Research Center for Neurological Diseases, Beijing, China.
  • Hicks B; Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, China.
  • Hutchinson A; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
  • Kirk E; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • Troester MA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • Li M; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
  • Shen Y; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • Ma T; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • Wang J; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
  • Liu X; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • Wang S; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
  • Gui S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • McMaster ML; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
  • Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • Parry DM; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
  • Goldstein AM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland.
  • Yang XR; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Clin Cancer Res ; 29(1): 261-270, 2023 01 04.
Article de En | MEDLINE | ID: mdl-36260525
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.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Chordome / Tumeurs de la base du crâne Type d'étude: Prognostic_studies / Risk_factors_studies Limites: Humans Langue: En Journal: Clin Cancer Res Sujet du journal: NEOPLASIAS Année: 2023 Type de document: Article Pays d'affiliation: Chine

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Chordome / Tumeurs de la base du crâne Type d'étude: Prognostic_studies / Risk_factors_studies Limites: Humans Langue: En Journal: Clin Cancer Res Sujet du journal: NEOPLASIAS Année: 2023 Type de document: Article Pays d'affiliation: Chine