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| Status |
Public on Jul 11, 2023 |
| Title |
DNA methylation, combined with RNA sequencing, provide novel insight into molecular classification of chordomas and their microenvironment |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Chordomas are rare tumors of notochord remnants, occurring mainly in the sacrum and skull base. Despite of their unusually slow growth, chordomas are highly invasive and the involvement of adjacent critical structures causes treatment challenges. Due to the low incidence, the molecular pathogenesis of this entity remains largely unknown. This study aimed to investigate DNA methylation abnormalities and their impact on gene expression profiles in skull base chordomas. 32 tumor and 4 normal nucleus pulposus samples were subjected to DNA methylation and gene expression profiling with methylation microarrays and RNA sequencing. Genome-wide DNA methylation analysis revealed two distinct clusters for chordoma (termed subtypes C and I) with different patterns of aberrant DNA methylation. C Chordomas were characterized by general hypomethylation with hypermethylation of CpG islands, while I chordomas were generally hypermethylated. These differences were reflected by distinct distribution of differentially methylated probes (DMPs). Differentially methylated regions (DMRs) were identified, indicating aberrant methylation in known tumor-related genes in booth chordoma subtypes and regions encoding small RNAs in subtype C chordomas. Correlation between methylation and expression was observed in a minority of genes. Upregulation of TBXT in chordomas appeared to be related to lower methylation of tumor-specific DMR in gene promoter. Gene expression-based clusters of tumor samples did not overlap with DNA methylation-based subtypes. Nevertheless, they differ in transcriptomic profile that shows immune infiltration in I chordomas and up-regulation of cell cycle in C chordomas. Immune enrichment in chordomas I was confirmed with 3 independent deconvolution methods and immunohistochemistry. Copy number analysis showed higher chromosomal instability in C chordomas. Nine out of eight had deletion of CDKN2A/B loci and downregulation of genes encoded in related chromosomal band. No significant difference in patients’ survival was observed between tumor subtypes, however, shorter survival was observed in patients with higher number of copy number alterations.
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| Overall design |
Comparative gene expression and DNA methylation between chordoma (32) and nucleus pulposus (4) samples
Kallisto expression quantification is available on GitHub:
https://github.com/SBaluszek/chordoma_RNA_met/blob/main/count_table.csv
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| Web link |
https://0-actaneurocomms-biomedcentral-com.brum.beds.ac.uk/articles/10.1186/s40478-023-01610-0
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| Contributor(s) |
Baluszek SP, Bujko M |
| Citation(s) |
37434245 |
| Submission date |
Apr 20, 2023 |
| Last update date |
Feb 12, 2024 |
| Contact name |
Szymon Piotr Baluszek |
| E-mail(s) |
szymon.baluszek@gmail.com
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| Organization name |
Maria Sklodowska-Curie National Research Institute of Oncology
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| Department |
Department of Molecular and Translational Oncology
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| Street address |
Wilhelma Konrada Roentgena 5
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| City |
Warsaw |
| State/province |
mazowieckie |
| ZIP/Postal code |
02-781 |
| Country |
Poland |
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| Platforms (1) |
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| Samples (36)
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| GSM7191098 |
20_17 sample, chordoma |
| GSM7191099 |
24_18 sample, chordoma |
| GSM7191100 |
26_15 sample, chordoma |
| GSM7191101 |
26_16 sample, chordoma |
| GSM7191102 |
28_20 sample, chordoma |
| GSM7191103 |
31_14 sample, chordoma |
| GSM7191104 |
31_20 sample, chordoma |
| GSM7191105 |
32_14 sample, chordoma |
| GSM7191106 |
35_17 sample, chordoma |
| GSM7191107 |
37_19 sample, chordoma |
| GSM7191108 |
38_17 sample, chordoma |
| GSM7191109 |
39_18 sample, chordoma |
| GSM7191110 |
4_19 sample, chordoma |
| GSM7191111 |
40_18 sample, chordoma |
| GSM7191112 |
45_17 sample, chordoma |
| GSM7191113 |
5_16 sample, chordoma |
| GSM7191114 |
50_15 sample, chordoma |
| GSM7191115 |
50_19 sample, chordoma |
| GSM7191117 |
53_18 sample, chordoma |
| GSM7191120 |
54_15 sample, chordoma |
| GSM7191121 |
55_19 sample, chordoma |
| GSM7191122 |
6_16 sample, chordoma |
| GSM7191123 |
62_15 sample, chordoma |
| GSM7191124 |
68_18 sample, chordoma |
| GSM7191125 |
7_19 sample, chordoma |
| GSM7191126 |
74_19 sample, chordoma |
| GSM7191127 |
81_15 sample, chordoma |
| GSM7191128 |
9_20 sample, chordoma |
| GSM7191129 |
92_15 sample, chordoma |
| GSM7191130 |
NP1 sample, nucleus pulposus |
| GSM7191131 |
NP4 sample, nucleus pulposus |
| GSM7191132 |
NP8 sample, nucleus pulposus |
| GSM7191133 |
NP9 sample, nucleus pulposus |
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| Relations |
| BioProject |
PRJNA957782 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE230168_RAW.tar |
161.2 Mb |
(http)(custom) |
TAR |
| GSE230168_m_values.csv.gz |
238.4 Mb |
(ftp)(http) |
CSV |
| GSE230168_matrix_signal.txt.gz |
157.2 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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