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GCT-52. TRANSCRIPTOME OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR REVEALS ITS PATHOGENESIS AND CONTRASTS WITH TESTICULAR COUNTERPARTS IN INTEGRATED OMICS ANALYSIS

Germ cell tumors (GCTs) are unique neoplasms in that they arise from the migrated cells which were supposed to be directed to gonads. They occur in the central nervous system (CNS), as well as gonadal organs such as testis and ovary. Our genomic analysis revealed that they are characterized by mutat...

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Autores principales: Takami, Hirokazu, Elzawahry, Asmaa, Kato, Mamoru, Fukuoka, Kohei, Mamatjan, Yasin, Suzuki, Tomonari, Yanagisawa, Takaaki, Matsushita, Yuko, Nakamura, Taishi, Yamasaki, Kai, Mukasa, Akitake, Saito, Nobuhito, Kanamori, Masayuki, Kumabe, Toshihiro, Tominaga, Teiji, Kobayashi, Keiichi, Nagane, Motoo, Iuchi, Toshihiko, Tamura, Kaoru, Maehara, Taketoshi, Sugiyama, Kazuhiko, Nakada, Mitsutoshi, Kanemura, Yonehiro, Nonaka, Masahiro, Asai, Akio, Yokogami, Kiyotaka, Takeshima, Hideo, Narita, Yoshitaka, Shibui, Soichiro, Nakazato, Yoichi, Totoki, Yasushi, Shibata, Tatsuhiro, Nishikawa, Ryo, Matsutani, Masao, Ichimura, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715891/
http://dx.doi.org/10.1093/neuonc/noaa222.270
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author Takami, Hirokazu
Elzawahry, Asmaa
Kato, Mamoru
Fukuoka, Kohei
Mamatjan, Yasin
Suzuki, Tomonari
Yanagisawa, Takaaki
Matsushita, Yuko
Nakamura, Taishi
Yamasaki, Kai
Mukasa, Akitake
Saito, Nobuhito
Kanamori, Masayuki
Kumabe, Toshihiro
Tominaga, Teiji
Kobayashi, Keiichi
Nagane, Motoo
Iuchi, Toshihiko
Tamura, Kaoru
Maehara, Taketoshi
Sugiyama, Kazuhiko
Nakada, Mitsutoshi
Kanemura, Yonehiro
Nonaka, Masahiro
Asai, Akio
Yokogami, Kiyotaka
Takeshima, Hideo
Narita, Yoshitaka
Shibui, Soichiro
Nakazato, Yoichi
Totoki, Yasushi
Shibata, Tatsuhiro
Nishikawa, Ryo
Matsutani, Masao
Ichimura, Koichi
author_facet Takami, Hirokazu
Elzawahry, Asmaa
Kato, Mamoru
Fukuoka, Kohei
Mamatjan, Yasin
Suzuki, Tomonari
Yanagisawa, Takaaki
Matsushita, Yuko
Nakamura, Taishi
Yamasaki, Kai
Mukasa, Akitake
Saito, Nobuhito
Kanamori, Masayuki
Kumabe, Toshihiro
Tominaga, Teiji
Kobayashi, Keiichi
Nagane, Motoo
Iuchi, Toshihiko
Tamura, Kaoru
Maehara, Taketoshi
Sugiyama, Kazuhiko
Nakada, Mitsutoshi
Kanemura, Yonehiro
Nonaka, Masahiro
Asai, Akio
Yokogami, Kiyotaka
Takeshima, Hideo
Narita, Yoshitaka
Shibui, Soichiro
Nakazato, Yoichi
Totoki, Yasushi
Shibata, Tatsuhiro
Nishikawa, Ryo
Matsutani, Masao
Ichimura, Koichi
author_sort Takami, Hirokazu
collection PubMed
description Germ cell tumors (GCTs) are unique neoplasms in that they arise from the migrated cells which were supposed to be directed to gonads. They occur in the central nervous system (CNS), as well as gonadal organs such as testis and ovary. Our genomic analysis revealed that they are characterized by mutations in MAPK and PI3K pathways, chromosomal instability and global hypomethylation in germinoma. However, there were plenty of cases which lacked driver alterations and their pathogenesis is yet to be fully unraveled. Here we aimed to uncover CNSGCT’s pathogenesis from a transcriptomic perspective. Genome-wide transcriptional analysis was performed for 58 CNS and 3 testicular GCTs. This demonstrated that germinoma had a transcriptional profile characteristic to primordial germ cells (PGCs) at early embryogenesis, whereas non-germinomatous germ cell tumors (NGGCTs) showed that with differentiation into various tissues. Integration of transcriptome and methylome corroborated the above finding that pluripotency/meiosis-genes were unmethylated and highly expressed in germinoma compared with NGGCT. Co-analysis with transcriptome of various developmental stages of embryonic cells revealed germinoma and NGGCT had similarities in expression to PGC and embryonic stem cells, respectively. Multi-omics analysis with testicular GCTs (n=134) from TCGA showed shared genomic backgrounds between germinoma-seminoma and NGGCT-nonseminomatous GCT (NSGCT) in mutation and methylation profiles, and contrast in the chromosomal instability, which was more highlighted in testicular GCTs. These new insights into molecular profiles of GCTs lead to a better understanding of the complex pathogenesis of GCTs, and will hopefully provide a clue to future development of new treatments.
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spelling pubmed-77158912020-12-09 GCT-52. TRANSCRIPTOME OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR REVEALS ITS PATHOGENESIS AND CONTRASTS WITH TESTICULAR COUNTERPARTS IN INTEGRATED OMICS ANALYSIS Takami, Hirokazu Elzawahry, Asmaa Kato, Mamoru Fukuoka, Kohei Mamatjan, Yasin Suzuki, Tomonari Yanagisawa, Takaaki Matsushita, Yuko Nakamura, Taishi Yamasaki, Kai Mukasa, Akitake Saito, Nobuhito Kanamori, Masayuki Kumabe, Toshihiro Tominaga, Teiji Kobayashi, Keiichi Nagane, Motoo Iuchi, Toshihiko Tamura, Kaoru Maehara, Taketoshi Sugiyama, Kazuhiko Nakada, Mitsutoshi Kanemura, Yonehiro Nonaka, Masahiro Asai, Akio Yokogami, Kiyotaka Takeshima, Hideo Narita, Yoshitaka Shibui, Soichiro Nakazato, Yoichi Totoki, Yasushi Shibata, Tatsuhiro Nishikawa, Ryo Matsutani, Masao Ichimura, Koichi Neuro Oncol Germ Cell Tumors Germ cell tumors (GCTs) are unique neoplasms in that they arise from the migrated cells which were supposed to be directed to gonads. They occur in the central nervous system (CNS), as well as gonadal organs such as testis and ovary. Our genomic analysis revealed that they are characterized by mutations in MAPK and PI3K pathways, chromosomal instability and global hypomethylation in germinoma. However, there were plenty of cases which lacked driver alterations and their pathogenesis is yet to be fully unraveled. Here we aimed to uncover CNSGCT’s pathogenesis from a transcriptomic perspective. Genome-wide transcriptional analysis was performed for 58 CNS and 3 testicular GCTs. This demonstrated that germinoma had a transcriptional profile characteristic to primordial germ cells (PGCs) at early embryogenesis, whereas non-germinomatous germ cell tumors (NGGCTs) showed that with differentiation into various tissues. Integration of transcriptome and methylome corroborated the above finding that pluripotency/meiosis-genes were unmethylated and highly expressed in germinoma compared with NGGCT. Co-analysis with transcriptome of various developmental stages of embryonic cells revealed germinoma and NGGCT had similarities in expression to PGC and embryonic stem cells, respectively. Multi-omics analysis with testicular GCTs (n=134) from TCGA showed shared genomic backgrounds between germinoma-seminoma and NGGCT-nonseminomatous GCT (NSGCT) in mutation and methylation profiles, and contrast in the chromosomal instability, which was more highlighted in testicular GCTs. These new insights into molecular profiles of GCTs lead to a better understanding of the complex pathogenesis of GCTs, and will hopefully provide a clue to future development of new treatments. Oxford University Press 2020-12-04 /pmc/articles/PMC7715891/ http://dx.doi.org/10.1093/neuonc/noaa222.270 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
Takami, Hirokazu
Elzawahry, Asmaa
Kato, Mamoru
Fukuoka, Kohei
Mamatjan, Yasin
Suzuki, Tomonari
Yanagisawa, Takaaki
Matsushita, Yuko
Nakamura, Taishi
Yamasaki, Kai
Mukasa, Akitake
Saito, Nobuhito
Kanamori, Masayuki
Kumabe, Toshihiro
Tominaga, Teiji
Kobayashi, Keiichi
Nagane, Motoo
Iuchi, Toshihiko
Tamura, Kaoru
Maehara, Taketoshi
Sugiyama, Kazuhiko
Nakada, Mitsutoshi
Kanemura, Yonehiro
Nonaka, Masahiro
Asai, Akio
Yokogami, Kiyotaka
Takeshima, Hideo
Narita, Yoshitaka
Shibui, Soichiro
Nakazato, Yoichi
Totoki, Yasushi
Shibata, Tatsuhiro
Nishikawa, Ryo
Matsutani, Masao
Ichimura, Koichi
GCT-52. TRANSCRIPTOME OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR REVEALS ITS PATHOGENESIS AND CONTRASTS WITH TESTICULAR COUNTERPARTS IN INTEGRATED OMICS ANALYSIS
title GCT-52. TRANSCRIPTOME OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR REVEALS ITS PATHOGENESIS AND CONTRASTS WITH TESTICULAR COUNTERPARTS IN INTEGRATED OMICS ANALYSIS
title_full GCT-52. TRANSCRIPTOME OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR REVEALS ITS PATHOGENESIS AND CONTRASTS WITH TESTICULAR COUNTERPARTS IN INTEGRATED OMICS ANALYSIS
title_fullStr GCT-52. TRANSCRIPTOME OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR REVEALS ITS PATHOGENESIS AND CONTRASTS WITH TESTICULAR COUNTERPARTS IN INTEGRATED OMICS ANALYSIS
title_full_unstemmed GCT-52. TRANSCRIPTOME OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR REVEALS ITS PATHOGENESIS AND CONTRASTS WITH TESTICULAR COUNTERPARTS IN INTEGRATED OMICS ANALYSIS
title_short GCT-52. TRANSCRIPTOME OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR REVEALS ITS PATHOGENESIS AND CONTRASTS WITH TESTICULAR COUNTERPARTS IN INTEGRATED OMICS ANALYSIS
title_sort gct-52. transcriptome of central nervous system germ cell tumor reveals its pathogenesis and contrasts with testicular counterparts in integrated omics analysis
topic Germ Cell Tumors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715891/
http://dx.doi.org/10.1093/neuonc/noaa222.270
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