Project description:Pediatric embryonal brain tumor (PEBT), which includes medulloblastoma (MB), primitive neuroectodermal tumor (PNET) and atypical teratoid/rhabdoid tumor (AT/RT), is the second most prevalent pediatric tumor type among brain tumors of childhood. AT/RT is highly malignant and is often misdiagnosed as MB and PNET. Distinguishing AT/RT from PNET/MB is of clinical significance since the survival rate of AT/RT patients is much lower. The diagnosis of AT/RT relies primarily on the morphologic assessment and immunohistochemistry (IHC) staining on a few known markers such as the lack of INI1 protein expression. However, in our clinical practice we observed several AT/RT-like tumors, which fulfilled histopathologic and all other biomarker criteria for AT/RT diagnosis, still showed retained INI1 immunoreactivity. Recent studies also reported retained INI1 immunoreactivity among certain diagnosed AT/RTs. It is therefore necessary to re-evaluate INI1(+), AT/RT-like cases. Sanger sequencing, array CGH and mRNA microarray analyses were performed on PEBT samples for studying their genomics landscapes. AT/RT and INI(+) AT/RT-like patients had similar survival rate, and global array CGH analysis and INI1 gene sequencing showed there is no differential chromosomal aberration marker between INI1(-) AT/RT and INI(+) AT/RT-like cases. We did not misdiagnose MB or PNET as AT/RT-like cases since transcriptome profiling revealed that not only AT/RT and INI(+) AT/RT-like cases expressed distinct mRNA and microRNA profiles, and their gene expression patterns were different from those of MBs and PNETs. AT/RTs shared the closest transcriptome profile to embryonic stem cells, INI1(+) AT/RT-like tumors were more similar to somatic neural stem cell, while MBs were closer to fetal brain. Novel biomarkers were identified to distinguish INI1(-) AT/RTs, INI1(+) AT/RT-like cases and MBs. Our studies disclosed a novel INI1(+) ATRT-like subtype among Taiwanese pediatric cases. New diagnostic biomarkers, as well as new therapeutic tactics, can be developed according to the transcriptome information unveiled in this work. 2 AT/RT-like cases and 7 AT/RT cases are subjected to transcriptome analysis.

Project description:Pediatric embryonal brain tumor (PEBT), which includes medulloblastoma (MB), primitive neuroectodermal tumor (PNET) and atypical teratoid/rhabdoid tumor (AT/RT), is the second most prevalent pediatric tumor type among brain tumors of childhood. AT/RT is highly malignant and is often misdiagnosed as MB and PNET. Distinguishing AT/RT from PNET/MB is of clinical significance since the survival rate of AT/RT patients is much lower. The diagnosis of AT/RT relies primarily on the morphologic assessment and immunohistochemistry (IHC) staining on a few known markers such as the lack of INI1 protein expression. However, in our clinical practice we observed several AT/RT-like tumors, which fulfilled histopathologic and all other biomarker criteria for AT/RT diagnosis, still showed retained INI1 immunoreactivity. Recent studies also reported retained INI1 immunoreactivity among certain diagnosed AT/RTs. It is therefore necessary to re-evaluate INI1(+), AT/RT-like cases. Sanger sequencing, array CGH and mRNA microarray analyses were performed on PEBT samples for studying their genomics landscapes. AT/RT and INI(+) AT/RT-like patients had similar survival rate, and global array CGH analysis and INI1 gene sequencing showed there is no differential chromosomal aberration marker between INI1(-) AT/RT and INI(+) AT/RT-like cases. We did not misdiagnose MB or PNET as AT/RT-like cases since transcriptome profiling revealed that not only AT/RT and INI(+) AT/RT-like cases expressed distinct mRNA and microRNA profiles, and their gene expression patterns were different from those of MBs and PNETs. AT/RTs shared the closest transcriptome profile to embryonic stem cells, INI1(+) AT/RT-like tumors were more similar to somatic neural stem cell, while MBs were closer to fetal brain. Novel biomarkers were identified to distinguish INI1(-) AT/RTs, INI1(+) AT/RT-like cases and MBs. Our studies disclosed a novel INI1(+) ATRT-like subtype among Taiwanese pediatric cases. New diagnostic biomarkers, as well as new therapeutic tactics, can be developed according to the transcriptome information unveiled in this work.

Dataset Information

Measles oncolytic virus as an immunotherapy for recurrent/refractory pediatric medulloblastoma and atypical teratoid rhabdoid tumor [scRNA-Seq]

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