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GCT-73. EXPRESSION PROFILING OF INTRACRANIAL GERM CELL TUMORS REVEALS UPREGULATION OF RAS THROUGH mRNA-microRNA SIGNALING PATHWAY
Intracranial germ cell tumors (IGCTs) account for 3% of CNS tumors in children in the U.S. and 11% in Japan and East Asian countries. IGCTs are separated into two distinct subtypes based on histology: germinomas and non-germinomatous germ cell tumors (NGGCTs). The deep central location of IGCTs make...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715349/ http://dx.doi.org/10.1093/neuonc/noaa222.289 |
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author | Taylor, Aaron M Shen, Jianhe Ren, Lingzhao Terashima, Keita Huang, Lei Snyder, Elizabeth M Adesina, Adekunle Su, Jack Nishikawa, Ryo Nakamura, Hideo Ng, Ho-Keung Wong, Stephen T C Braun, Robert E Man, Tsz-Kwong Lau, Ching C |
author_facet | Taylor, Aaron M Shen, Jianhe Ren, Lingzhao Terashima, Keita Huang, Lei Snyder, Elizabeth M Adesina, Adekunle Su, Jack Nishikawa, Ryo Nakamura, Hideo Ng, Ho-Keung Wong, Stephen T C Braun, Robert E Man, Tsz-Kwong Lau, Ching C |
author_sort | Taylor, Aaron M |
collection | PubMed |
description | Intracranial germ cell tumors (IGCTs) account for 3% of CNS tumors in children in the U.S. and 11% in Japan and East Asian countries. IGCTs are separated into two distinct subtypes based on histology: germinomas and non-germinomatous germ cell tumors (NGGCTs). The deep central location of IGCTs makes surgical resection and therefore molecular subtype classification difficult, and previous gene expression studies are limited. We performed mRNA expression profiling (Human Genome U133 Plus 2.0) and microRNA expression profiling (ABI TaqMan) with 36 and 49 IGCTs, respectively. Sample stratification using non-negative matrix factorization clustering of gene expression revealed two distinct subgroups that delineated germinomas from NGGCTs. Employing stepwise model building in each data set separately, we were able to separate these groups using only mRNA probes for the LIN28B and L1TD1 genes, and two microRNA, microRNA-26a and microRNA-373. MicroRNA26a suppresses the LIN28B gene and is down-regulated in germinoma. LIN28B directly binds and suppresses the let-7 microRNA family, which suppress the KRAS oncogene, previously found to be mutated in ~19% of IGCTs. L1TD1 is required for human stem cell renewal and directly interacts with LIN28B for its RNA binding function. LIN28B and L1TD1 are both known to be upregulated in other systemic germ cell tumors, but this has not yet been documented in IGCTs. In conclusion, these results show that intracranial germinomas have similar gene expression compared to systemic seminoma, and suggest a mechanism by which activation of LIN28B and L1TD1 downregulates the let-7 microRNA and subsequently upregulates KRAS. |
format | Online Article Text |
id | pubmed-7715349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77153492020-12-09 GCT-73. EXPRESSION PROFILING OF INTRACRANIAL GERM CELL TUMORS REVEALS UPREGULATION OF RAS THROUGH mRNA-microRNA SIGNALING PATHWAY Taylor, Aaron M Shen, Jianhe Ren, Lingzhao Terashima, Keita Huang, Lei Snyder, Elizabeth M Adesina, Adekunle Su, Jack Nishikawa, Ryo Nakamura, Hideo Ng, Ho-Keung Wong, Stephen T C Braun, Robert E Man, Tsz-Kwong Lau, Ching C Neuro Oncol Germ Cell Tumors Intracranial germ cell tumors (IGCTs) account for 3% of CNS tumors in children in the U.S. and 11% in Japan and East Asian countries. IGCTs are separated into two distinct subtypes based on histology: germinomas and non-germinomatous germ cell tumors (NGGCTs). The deep central location of IGCTs makes surgical resection and therefore molecular subtype classification difficult, and previous gene expression studies are limited. We performed mRNA expression profiling (Human Genome U133 Plus 2.0) and microRNA expression profiling (ABI TaqMan) with 36 and 49 IGCTs, respectively. Sample stratification using non-negative matrix factorization clustering of gene expression revealed two distinct subgroups that delineated germinomas from NGGCTs. Employing stepwise model building in each data set separately, we were able to separate these groups using only mRNA probes for the LIN28B and L1TD1 genes, and two microRNA, microRNA-26a and microRNA-373. MicroRNA26a suppresses the LIN28B gene and is down-regulated in germinoma. LIN28B directly binds and suppresses the let-7 microRNA family, which suppress the KRAS oncogene, previously found to be mutated in ~19% of IGCTs. L1TD1 is required for human stem cell renewal and directly interacts with LIN28B for its RNA binding function. LIN28B and L1TD1 are both known to be upregulated in other systemic germ cell tumors, but this has not yet been documented in IGCTs. In conclusion, these results show that intracranial germinomas have similar gene expression compared to systemic seminoma, and suggest a mechanism by which activation of LIN28B and L1TD1 downregulates the let-7 microRNA and subsequently upregulates KRAS. Oxford University Press 2020-12-04 /pmc/articles/PMC7715349/ http://dx.doi.org/10.1093/neuonc/noaa222.289 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Germ Cell Tumors Taylor, Aaron M Shen, Jianhe Ren, Lingzhao Terashima, Keita Huang, Lei Snyder, Elizabeth M Adesina, Adekunle Su, Jack Nishikawa, Ryo Nakamura, Hideo Ng, Ho-Keung Wong, Stephen T C Braun, Robert E Man, Tsz-Kwong Lau, Ching C GCT-73. EXPRESSION PROFILING OF INTRACRANIAL GERM CELL TUMORS REVEALS UPREGULATION OF RAS THROUGH mRNA-microRNA SIGNALING PATHWAY |
title | GCT-73. EXPRESSION PROFILING OF INTRACRANIAL GERM CELL TUMORS REVEALS UPREGULATION OF RAS THROUGH mRNA-microRNA SIGNALING PATHWAY |
title_full | GCT-73. EXPRESSION PROFILING OF INTRACRANIAL GERM CELL TUMORS REVEALS UPREGULATION OF RAS THROUGH mRNA-microRNA SIGNALING PATHWAY |
title_fullStr | GCT-73. EXPRESSION PROFILING OF INTRACRANIAL GERM CELL TUMORS REVEALS UPREGULATION OF RAS THROUGH mRNA-microRNA SIGNALING PATHWAY |
title_full_unstemmed | GCT-73. EXPRESSION PROFILING OF INTRACRANIAL GERM CELL TUMORS REVEALS UPREGULATION OF RAS THROUGH mRNA-microRNA SIGNALING PATHWAY |
title_short | GCT-73. EXPRESSION PROFILING OF INTRACRANIAL GERM CELL TUMORS REVEALS UPREGULATION OF RAS THROUGH mRNA-microRNA SIGNALING PATHWAY |
title_sort | gct-73. expression profiling of intracranial germ cell tumors reveals upregulation of ras through mrna-microrna signaling pathway |
topic | Germ Cell Tumors |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715349/ http://dx.doi.org/10.1093/neuonc/noaa222.289 |
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