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| Status |
Public on Apr 25, 2023 |
| Title |
Exceptionally rare IDH1-mutant adult medulloblastoma with concurrent GNAS mutation revealed by in vivo magnetic resonance spectroscopy and deep sequencing |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adult. Based on transcriptome profile MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate Dehydrogenase-1 (IDH1) mutations have been described in several tumours, including gliomas, while in MB are exceptionally reported and not routinely investigated. By mean of magnetic resonance spectroscopy (MRS) we unequivocally assessed the presence the oncometabolite D-2-Hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutation, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also exceptionally described in MB. To our knowledge this is the first reported case of MB harboring both mutations together. Of note, tumour exhibited a heterogeneous phenotype with a tumour component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting coexistence of two different major tumour clones. These findings draw attention to the need of a deeper genetic characterization of MB in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, reported data underling the importance of performing MRS for the identification of IDH mutations in non-glial tumours. The use of throughput molecular profiling analysis and advanced medical imaging technology will certainly increase the frequency with which rare tumour entities will be identified. Whether they have any particular therapeutic implications or prognostic relevance requires further investigations.
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| Overall design |
Tumor case report
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| Contributor(s) |
Miele E |
| Citation(s) |
36941703 |
| Submission date |
Feb 14, 2023 |
| Last update date |
Apr 26, 2023 |
| Contact name |
Evelina Miele |
| E-mail(s) |
evelina.miele@opbg.net
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| Organization name |
Ospedale Pediatrico Bambino Gesù
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| Department |
Oncoematologia
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| Street address |
Piazza di Sant'Onofrio 4
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| City |
Rome |
| ZIP/Postal code |
00165 |
| Country |
Italy |
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| Platforms (1) |
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| Samples (1) |
| GSM7043831 |
Exceptionally rare IDH1-mutant adult medulloblastoma with concurrent GNAS mutation |
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| Relations |
| BioProject |
PRJNA934923 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE225302_RAW.tar |
175.1 Mb |
(http)(custom) |
TAR (of IDAT) |
| GSE225302_signal_intensities.txt.gz |
6.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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