Genomic profiles and clinical presentation of chordoma

Chordoma is a rare bone cancer with variable clinical outcomes. Here, we recruited 184 sporadic chordoma patients from the US and Canada and collected their clinical and treatment data. The average age at diagnosis was 45.5 years (Range 5-78) and the chordoma site distribution was 49.2% clivus, 26.2% spinal, and 24.0% sacral. Most patients (97.5%) received surgery as the primary treatment, among whom 85.3% also received additional treatment. Except for the most prevalent cancers like prostate, lung, breast, and skin cancer, there was no discernible enrichment for any specific cancer type among patients or their family members. Among a subset of patients (N = 70) with tumor materials, we conducted omics analyses and obtained targeted panel sequencing and SNP array genotyping data for 51 and 49 patients, respectively. The most recurrent somatic driver mutations included PIK3CA (12%), followed by chromatin remodeling genes PBRM1 and SETD2. Amplification of the 6q27 region, containing the chordoma susceptibility gene TBXT, was detected in eight patients (16.3%). Clival patients appeared to be less likely to carry driver gene mutations, chromosome arm level deletion events (e.g., 5p, 5p, and 9p), or 6q27 amplification compared to sacral patients. After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96-96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77-105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression.

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Publication Details

Journal
Acta Neuropathologica Communications
Published
2024-08-12
DOI
https://doi.org/10.1186/s40478-024-01833-9
Citations
8
Primary Topic
Bone Tumor Diagnosis and Treatments
Type
article
Field-Weighted Citation Impact
3.76

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article

Genomic profiles and clinical presentation of chordoma

Alyssa Klein, Dilys M. Parry, Xing Hua, Wen Luo et al.
8 citations
Acta Neuropathologica Communications
Bone Tumor Diagnosis and Treatments
3.76
article

Genomic profiles and clinical presentation of chordoma

Alyssa Klein, Dilys M. Parry, Xing Hua, Wen Luo, Jiwei Bai, Xiaohong R. Yang, Kristine M. Jones, Yujia Xiong, Mary L. McMaster, Alisa M. Goldstein, Tongwu Zhang, Weiyin Zhou, Belynda D. Hicks, Hela Koka, Difei Wang, Aurélie Vogt, Xin Li
article en
8 citations

Abstract

Chordoma is a rare bone cancer with variable clinical outcomes. Here, we recruited 184 sporadic chordoma patients from the US and Canada and collected their clinical and treatment data. The average age at diagnosis was 45.5 years (Range 5-78) and the chordoma site distribution was 49.2% clivus, 26.2% spinal, and 24.0% sacral. Most patients (97.5%) received surgery as the primary treatment, among whom 85.3% also received additional treatment. Except for the most prevalent cancers like prostate, lung, breast, and skin cancer, there was no discernible enrichment for any specific cancer type among patients or their family members. Among a subset of patients (N = 70) with tumor materials, we conducted omics analyses and obtained targeted panel sequencing and SNP array genotyping data for 51 and 49 patients, respectively. The most recurrent somatic driver mutations included PIK3CA (12%), followed by chromatin remodeling genes PBRM1 and SETD2. Amplification of the 6q27 region, containing the chordoma susceptibility gene TBXT, was detected in eight patients (16.3%). Clival patients appeared to be less likely to carry driver gene mutations, chromosome arm level deletion events (e.g., 5p, 5p, and 9p), or 6q27 amplification compared to sacral patients. After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96-96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77-105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression.

Acta Neuropathologica CommunicationsVol. 12(1)
Leidos (United States) (US), National Institutes of Health (US), Capital Medical University (CN), Sichuan University (CN), Beijing Tian Tan Hospital (CN), West China Hospital of Sichuan University (CN), Frederick National Laboratory for Cancer Research (US), National Cancer Institute (US), Department of Health and Human Services (US)
Chordoma Foundation, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 7%
Bone Tumor Diagnosis and Treatments
3.76
DOIOpen Access PDFOpenAlex
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