Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel.
The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human di...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296699&type=printable |
| _version_ | 1797315935266144256 |
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| author | Ashley M Brooks Andrea Vornoli Ramesh C Kovi Thai Vu T Ton Miaofei Xu Ahmed Mashal Eva Tibaldi Federica Gnudi Jian-Liang Li Robert C Sills John R Bucher Daniele Mandrioli Fiorella Belpoggi Arun R Pandiri |
| author_facet | Ashley M Brooks Andrea Vornoli Ramesh C Kovi Thai Vu T Ton Miaofei Xu Ahmed Mashal Eva Tibaldi Federica Gnudi Jian-Liang Li Robert C Sills John R Bucher Daniele Mandrioli Fiorella Belpoggi Arun R Pandiri |
| author_sort | Ashley M Brooks |
| collection | DOAJ |
| description | The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays. |
| first_indexed | 2024-03-08T03:11:04Z |
| format | Article |
| id | doaj.art-b685aa37cc7a40f4be53d0cfd6f31d19 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-08T03:11:04Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b685aa37cc7a40f4be53d0cfd6f31d192024-02-13T05:34:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029669910.1371/journal.pone.0296699Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel.Ashley M BrooksAndrea VornoliRamesh C KoviThai Vu T TonMiaofei XuAhmed MashalEva TibaldiFederica GnudiJian-Liang LiRobert C SillsJohn R BucherDaniele MandrioliFiorella BelpoggiArun R PandiriThe cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296699&type=printable |
| spellingShingle | Ashley M Brooks Andrea Vornoli Ramesh C Kovi Thai Vu T Ton Miaofei Xu Ahmed Mashal Eva Tibaldi Federica Gnudi Jian-Liang Li Robert C Sills John R Bucher Daniele Mandrioli Fiorella Belpoggi Arun R Pandiri Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel. PLoS ONE |
| title | Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel. |
| title_full | Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel. |
| title_fullStr | Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel. |
| title_full_unstemmed | Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel. |
| title_short | Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel. |
| title_sort | genetic profiling of rat gliomas and cardiac schwannomas from life time radiofrequency radiation exposure study using a targeted next generation sequencing gene panel |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296699&type=printable |
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