NBDC Research ID: hum0006.v6
SUMMARY
Aims: The identification of genomic/genetic alterations in brain tumors (gliomas) and analysis of their clinicopathological significance.
Brain tumors are diseases with a very poor prognosis and recurrence is almost inevitable even with multidisciplinary treatment. Therefore, it is important to elucidate genetic aberrations associated with the development or malignant transformation of brain tumors. In this study, we will comprehensively analyze molecular landscapes in brain tumors. We will also investigate how these are involved in the response to various therapies to establish new molecular therapies for brain tumors. In addition, we will develop new diagnostic methods and biomarkers by comparing clinicopathological information with molecular profiles and analyze the relationship between diagnosis, prognosis prediction, and therapeutic response prediction using bioinformatics and artificial intelligence.
Methods: Exome sequencing, RNA sequencing and Methylation array were performed. Matched normal DNA was also used for Exome sequencing.
Targeted DNA sequencing for vascular malformation samples was conducted to investigate somatic mutations.
FLeCS-seq, SMART-seq, RNA-seq, short-read WGS, and ultralong-read WGS analyses for normal left frontal lobe tissues were performed.
Participants/Materials:
Surgical specimen obtained from 6 patients with astrocytoma (primary and matched recurrent samples) and paired normal peripheral blood cells (total: 23 samples).
Surgical specimen obtained from 16 patients with oligodendroglioma (12 primary and matched recurrent samples, 8 samples obtained from 4 patients by multi-sampling)
Surgical specimen obtained from patients with gliomas (17 patients with diffuse cerebellar glioma, 8 patients with cerebral glioblastoma and 14 patients with thalamic glioma)
Surgical specimen obtained from 94 patients with gliomas, including primary and matched recurrent samples (total 114 samples) and paired normal blood cells
Twelve cerebral cavernous malformations, 1 vertebral hemangioma, 3 orbital cavernous malformations, and respective paired peripheral blood samples
Normal left frontal lobe tissues from a patient with glioma
| Dataset ID | Type of Data | Criteria | Release Date |
|---|---|---|---|
| JGAS000004 |
astrocytoma NGS (Exome) |
Controlled-access (Type I) | 2014/01/31 |
| JGAS000004 data addition |
oligodendroglioma NGS (Exome, RNA-seq), Methylation array |
Controlled-access (Type I) | 2017/06/05 |
| JGAS000106 |
gliomas (diffuse cerebellar glioma, cerebral glioblastoma, thalamic glioma) NGS (Exome, RNA-seq), Methylation array |
Controlled-access (Type I) | 2017/09/01 |
| JGAS000146 |
gliomas NGS (Exome, RNA-seq), Methylation array |
Controlled-access (Type I) | 2019/02/13 |
| JGAS000325 | NGS (Target Capture) | Controlled-access (Type I) | 2022/08/08 |
| JGAS000877 |
NGS（FLeCS-seq, SMART-seq, RNA-seq, short-read WGS, ultralong-read WGS） |
Controlled-access (Type I) | 2026/06/03 |
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MOLECULAR DATA
| Participants/Materials |
astrocytoma (ICD10: C71): 6 cases (23 samples) oligodendroglioma (ICD10: C71): 16 cases (48 samples) diffuse cerebellar glioma (ICD10: C71): 17 cases (34 samples) glioma (ICD10: C71): 12 cases (25 tumor samples, 12 non-tumor samples) 11 pairs of primary-recurrent gliomas and 1 primary glioma |
| Targets | Exome |
| Target Loci for Capture Methods | - |
| Platform | Illumina [HiSeq 2000] |
| Library Source | DNAs extracted from surgical specimen of brain tumors (primary and matched recurrent samples) and paired normal peripheral blood cells. |
| Cell Lines | - |
| Library Construction (kit name) | Agilent SureSelect Human All Exon v.4 |
| Fragmentation Methods | Ultrasonic fragmentation (Covaris SS) |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 100 bp |
| Japanese Genotype-phenotype Archive Dataset ID |
JGAD000004 (astrocytoma) JGAD000106 (oligodendroglioma) JGAD000112 (diffuse cerebellar glioma) JGAD000215 (primary grade II/III gliomas and their recurrent tumors; 36 samples, matched normal blood; 16 samples) JGAD000218 (primary grade IV gliomas and their recurrent tumors; 16 samples, matched normal blood; 8 samples) |
| Total Data Volume |
JGAD000004: 375.31 GB (fastq, bam [reference: hg19]) JGAD000106: 885.30 GB (fastq, bam [reference: hg19]) JGAD000112: 506.99 GB (fastq, bam [reference: hg19]) JGAD000215: 1.32 TB (fastq, bam [reference: hg19]) JGAD000218: 552.72 GB (fastq, bam [reference: hg19]) |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
oligodendroglioma (ICD10: C71): 16 cases (27 samples) diffuse cerebellar glioma (ICD10: C71): 14 cases (14 samples) cerebral glioblastoma (ICD10: C71): 8 cases (8 samples) glioma (ICD10: C71): 24 cases (31 samples) 8 pairs of primary-recurrent gliomas, 8 primary gliomas, and 7 recurrent gliomas |
| Targets | RNA-seq |
| Target Loci for Capture Methods | - |
| Platform | Illumina [HiSeq 2000] |
| Library Source | RNAs extracted from surgical specimen of brain tumors (primary and matched recurrent samples) and paired normal peripheral blood cells. |
| Cell Lines | - |
| Library Construction (kit name) | TruSeq Stranded Total RNA Library Prep Kit |
| Fragmentation Methods | Alkalization |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 100 bp |
| Japanese Genotype-phenotype Archive Dataset ID |
JGAD000113 (diffuse cerebellar glioma, cerebral glioblastoma) JGAD000216 (gliomas including primary grade II/III gliomas and their recurrent tumors; 31 samples) JGAD000219 (recurrent tumors of primary grade IV gliomas; 8 samples) |
| Total Data Volume |
JGAD000107: 239.26 GB (bam, fastq） JGAD000113: 363.23 GB (bam, fastq） JGAD000216: 302.43 GB (bam, fastq） JGAD000219: 96.94 GB (bam, fastq） |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
oligodendroglioma (ICD10: C71): 16 cases (30 samples) diffuse cerebellar glioma (ICD10: C71): 17 cases (17 samples) thalamic glioma (ICD10: C71): 14 cases (14 samples) glioma (ICD10: C71): 93 cases (113 samples) 20 pairs of primary-recurrent gliomas, 69 primary gliomas, and 4 recurrent gliomas |
| Targets | Methylation array |
| Target Loci for Capture Methods | - |
| Platform | Illumina [HumanMethylation 450 BeadChip] |
| Library Source | DNAs extracted from surgical specimen of brain tumors (primary and matched recurrent samples) and paired normal peripheral blood cells. |
| Cell Lines | - |
| Reagents (Kit, Version) | Illumina HumanMethylation450 BeadChip kit |
| Algorithms for Calculating Methylation-rate (software) | Genome Studio v2010.3 |
| Filtering Methods | HumanMethylation450_15017482_v1.1 (bpm) |
| Probe Number (after QC) | 485577 methylation sites |
| Japanese Genotype-phenotype Archive Dataset ID |
JGAD000114 (diffuse cerebellar glioma, thalamic glioma) JGAD000217 (gliomas including primary grade II/III tumors and their recurrent tumors; 113 samples) |
| Total Data Volume |
JGAD000108: 139.75 MB (txt) JGAD000114: 154.82 MB (txt) JGAD000217: 398.82 MB (txt) |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
cerebral cavernous malformation (ICD10：D180): 12 cases vertebral hemangioma (ICD10：D180): 1 cases orbital cavernous malformation (ICD10：D180): 3 cases vascular malformation samples, respective paired peripheral blood samples (total 32 samples) |
| Targets | Target Capture |
| Target Loci for Capture Methods | 6110 target genes |
| Platform | Illumina [HiSeq 2500] |
| Library Source | DNAs extracted from vascular malformation samples and respective paired peripheral blood samples |
| Cell Lines | - |
| Library Construction (kit name) | Agilent SureSelect XT Focused Exome target enrichment kit |
| Fragmentation Methods | Ultrasonic fragmentation (Covaris E220) |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 100 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000436 |
| Total Data Volume | 193.9 GB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials | glioma (ICD10: C71)：1 case (2 samples) |
| Targets | FLeCS-seq |
| Target Loci for Capture Methods | - |
| Platform | Nanopore [PromethION] |
| Library Source | RNAs extracted from normal left frontal lobe tissue |
| Cell Lines | - |
| Library Construction (kit name) | Ligation Sequencing Kit V14 |
| Fragmentation Methods | - |
| Spot Type | Single-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | - |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD001020 |
| Total Data Volume | 752.5 GB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials | glioma (ICD10: C71)：1 case (1 sample) |
| Targets | SMART-seq |
| Target Loci for Capture Methods | - |
| Platform | Nanopore [PromethION] |
| Library Source | RNAs extracted from normal left frontal lobe tissue |
| Cell Lines | - |
| Library Construction (kit name) | SMART-Seq mRNA Long Read, Ligation Sequencing Kit V14 |
| Fragmentation Methods | - |
| Spot Type | Single-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | - |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD001020 |
| Total Data Volume | 752.5 GB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials | glioma (ICD10: C71)：1 case (2 samples) |
| Targets | RNA-seq |
| Target Loci for Capture Methods | - |
| Platform | Element [AVITI] |
| Library Source | RNAs extracted from normal left frontal lobe tissue |
| Cell Lines | - |
| Library Construction (kit name) | SMART-seq stranded Kit |
| Fragmentation Methods | Heat treatment in the presence of Mg2+ |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 300 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD001020 |
| Total Data Volume | 752.5 GB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials | glioma (ICD10: C71)：1 case (1 sample) |
| Targets | short-read WGS |
| Target Loci for Capture Methods | - |
| Platform | Illumina [NovaSeq 6000] |
| Library Source | RNAs extracted from normal left frontal lobe tissue |
| Cell Lines | - |
| Library Construction (kit name) | TruSeq Nano DNA Library Prep Kit |
| Fragmentation Methods | Ultrasonic fragmentation |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 300 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD001020 |
| Total Data Volume | 752.5 GB (fastq) |
| Comments (Policies) | NBDC policy |
ultralong-read WGS (JGAS000877)
| Participants/Materials | glioma (ICD10: C71)：1 case (1 sample) |
| Targets | ultralong-read WGS |
| Target Loci for Capture Methods | - |
| Platform | Nanopore [PromethION] |
| Library Source | DNAs extracted from normal left frontal lobe tissue |
| Cell Lines | - |
| Library Construction (kit name) | Monarch HMW DNA Extraction Kit for Tissue、Ultra-Long DNA Sequencing Kit V14 |
| Fragmentation Methods | - |
| Spot Type | Single-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | - |
| Mapping Methods | minimap2 (Dorado) |
| Mapping Quality | Mapping rate 98.6% |
| Reference Genome Sequence | hg38 (reference_accession: GCF_000001405.26) |
| Coverage (Depth) | 44x |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD001020 |
| Total Data Volume | 752.5 GB (bam) |
| Comments (Policies) | NBDC policy |
DATA PROVIDER
Principal Investigator: Nobuhito Saito
Affiliation: Department of Neurosurgery, The University of Tokyo
Project / Group Name: Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT)
URL: http://p-direct.jfcr.or.jp/english/
Funds / Grants (Research Project Number):
| Name | Title | Project Number |
|---|---|---|
| Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT), Japan Agency for Medical Research and Development (AMED) | Development of novel therapeutic strategy and biomarker for the treatment of malignant brain tumors | - |
| Project for Cancer Research and Therapeutic Evolution (P-CREATE), Japan Agency for Medical Research and Development (AMED) | Analysis of the mechanisms for development of tumor heterogeneity related to treatment resistance of gliomas and discovery of therapeutic strategies | - |
| KAKENHI Grant-in-Aid for Scientific Research (B) | Analysis of novel vascular malformation causative gene | 21H03041 |
PUBLICATIONS
| Title | DOI | Dataset ID | |
|---|---|---|---|
| 1 | Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma | doi:10.1126/science.1239947 | JGAD000004 |
| 2 | Genetic and epigenetic stability of oligodendrogliomas at recurrence | doi: 10.1186/s40478-017-0422-z | JGAD000106-JGAD000108 |
| 3 | Distinct molecular profile of diffuse cerebellar gliomas | doi: 10.1007/s00401-017-1771-1 | JGAD000112-JGAD000113 |
| 4 | DNA demethylation is associated with malignant progression of lower-grade gliomas | doi: 10.1038/s41598-019-38510-0 | JGAD000215-JGAD000219 |
| 5 | Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations | doi: 10.1007/s10456-022-09846-5 | JGAD000436 |
USERS (Controlled-access Data)
| Principal Investigator | Affiliation | Country/Region | Research Title | Data in Use (Dataset ID) | Period of Data Use |
|---|---|---|---|---|---|
| Michiaki Hamada | Faculty of Science and Engineering, Waseda University | Japan | Construction of RNA-targeted Drug Discovery Database | JGAD000107 JGAD000113 JGAD000216 JGAD000219 |
2022/12/26-2027/10/31 |
| Frank Attenello | Keck School of Medicine of USC | United States of America | Examining the role of a novel long noncoding RNA, linc02454, in resistance of glioblastoma to temozolomide | JGAD000215-JGAD000219 | 2023/03/19-2026/01/31 |
