Study: JGAS00000000106

Identifier

AccessionJGAS00000000106

Description

TitleMolecular analysis of diffuse cerebellar gliomas
AbstractAmong diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients. World Health Organization histological grade at recurrence was mostly stable; it was increased in 2, the same in 9, and decreased in 1 cases. Whole-exome sequencing demonstrated that the rate of shared mutation between the primary and recurrent tumors was relatively low, ranging from 3.2-57.9% (average, 33.3%), indicating a branched evolutionary pattern. The trunk alterations that existed throughout the course were restricted to IDH1 mutation, 1p/19q-codeletion, and TERT promoter mutation, and mutation of the known candidate tumor suppressor genes CIC and FUBP1 were not consistently observed between primary and recurrent tumors. Multiple sampling from different regions within a tumor showed marked intratumoral heterogeneity. Notably, in general, the number of mutations was not significantly different after recurrence, remaining under 100, and no hypermutator phenotype was observed. FUBP1 mutation, loss of chr. 9p21, and TCF12 mutation were among a few recurrent de novo alterations that were found at recurrence, indicating that these events were clonally selected at recurrence but were not enough to enhance malignancy. Genome-wide methylation status, measured by Illumina 450 K arrays, was stable between recurrence and the primary tumor. In summary, although oligodendroglioma displays marked mutational heterogeneity, histological malignant transformation accompanying events such as considerable increase in mutation number and epigenetic profile change were not observed at recurrence, indicating that noticeable temporal and spatial genetic heterogeneity in oligodendrogliomas does not result in rapid tumor progression.
Study Type 1
Study TypeTumor vs. Matched-Normal
Study Type 2
Study TypeExome Sequencing
Study Type 3
Study TypeTranscriptome Sequencing
Study Type 4
Study TypeOther
New Study TypeDNA methylation array

Grant

Grant 1
TitleIdentification of new molecular targets with profiling of malignant mesothelioma / Development of therapeutic modalities against intractable cancers via identification of new therapeutic targets with molecular profiling / P-DIRECT: Project for Development of Innovative Research on Cancer Therapeutics
AgencyMinistry of Education, Culture, Sports, Science and Technology (MEXT)
Grant ID
Grant 2
TitleIdentification of new molecular targets with profiling of malignant mesothelioma / Development of therapeutic modalities against intractable cancers via identification of new therapeutic targets with molecular profiling / P-DIRECT: Project for Development of Innovative Research on Cancer Therapeutics
AgencyJapan Agency for Medical Research and Development (AMED)
Grant ID

Publication

Publication 1
PubMed ID28852847
Publication Statuspublished
DB TypePUBMED
Publication 2
PubMed ID24336570
Publication Statuspublished
DB TypePUBMED
Publication 3
PubMed ID28270234
Publication Statuspublished
DB TypePUBMED

Study Attribute

NBDC Numberhum0006
Registration date2017-06-02
Submitting organizationDepartment of Neurosurgery, The University of Tokyo
Principal InvestigatorNobuhito Saito
Molecular Data TypeExome sequencing
PlatformHiSeq 2000
VendorIllumina
Comment
Molecular Data TypeTranscriptome profiling by high-throughput sequencing
PlatformHiSeq 2000
VendorIllumina
Comment
Molecular Data TypeMethylation profiling by array
PlatformInfinium HumanMethylation450 BeadChip
VendorIllumina
Comment
Primary PhenotypeGlioma
Disease TypeNeoplasms
Cancer TypeGlioma
Dataset
Accession Title Dataset type Data objects Policy
JGAD00000000112 Exome of 17 Diffuse Cerebellar glioma and matched-normal from peripheral blood Exome sequencing 68 JGAP00000000004
JGAD00000000113 RNAseq of 14 Diffuse Cerebellar glioma and 8 Cerebral Glioblastoma Transcriptome profiling by high-throughput sequencing 44 JGAP00000000004
JGAD00000000114 DNA-methylation array of 17 Diffuse Cerebellar glioma and 14 Thalamic glioma 0 JGAP00000000004