Genomic profiles and clinical presentation of chordoma.
Humans
Chordoma
/ genetics
Male
Female
Middle Aged
Aged
Adult
Adolescent
Young Adult
Child
Child, Preschool
DNA-Binding Proteins
/ genetics
Mutation
Class I Phosphatidylinositol 3-Kinases
/ genetics
T-Box Domain Proteins
/ genetics
Transcription Factors
/ genetics
Nuclear Proteins
/ genetics
Skull Base Neoplasms
/ genetics
Spinal Neoplasms
/ genetics
Canada
Polymorphism, Single Nucleotide
Fetal Proteins
Histone-Lysine N-Methyltransferase
Chordoma
Chordoma sites
Clinical outcome
Genomic landscape
Treatment
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
12 Aug 2024
12 Aug 2024
Historique:
received:
24
04
2024
accepted:
30
06
2024
medline:
13
8
2024
pubmed:
13
8
2024
entrez:
12
8
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39135136
doi: 10.1186/s40478-024-01833-9
pii: 10.1186/s40478-024-01833-9
doi:
Substances chimiques
PIK3CA protein, human
EC 2.7.1.137
SETD2 protein, human
EC 2.1.1.43
DNA-Binding Proteins
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PBRM1 protein, human
0
T-Box Domain Proteins
0
Transcription Factors
0
Brachyury protein
EQ43SC3GDB
Nuclear Proteins
0
Fetal Proteins
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
129Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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