Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions
Abstract Dysembryoplastic neuroepithelial tumor (DNET) is a low-grade brain tumor commonly associated with drug-resistant epilepsy. About half of DNETs are accompanied by tiny nodular lesions separated from the main mass. The existence of these satellite lesions (SLs) has shown a strong association...
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26636-7 |
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| author | Yeajina Lee Jeyul Yang Seung Ah Choi Seung‐Ki Kim Sung-Hye Park Hyun Joo Park Jong-Il Kim Ji Hoon Phi |
| author_facet | Yeajina Lee Jeyul Yang Seung Ah Choi Seung‐Ki Kim Sung-Hye Park Hyun Joo Park Jong-Il Kim Ji Hoon Phi |
| author_sort | Yeajina Lee |
| collection | DOAJ |
| description | Abstract Dysembryoplastic neuroepithelial tumor (DNET) is a low-grade brain tumor commonly associated with drug-resistant epilepsy. About half of DNETs are accompanied by tiny nodular lesions separated from the main mass. The existence of these satellite lesions (SLs) has shown a strong association with tumor recurrence, suggesting that they are true tumors. However, it is not known whether SLs represent multiple foci of progenitor tumor cell extension and migration or a multifocal development of the main DNET. This study was designed to elucidate the histopathology and pathogenesis of SLs in DNETs. Separate biopsies from the main masses and SLs with DNET were analyzed. We performed comparative lesion sequencing and phylogenetic analysis. FGFR1 K656E and K655I mutations or duplication of the tyrosine kinase domain was found in all 3 DNET patients and the main masses and their SLs shared the same FGFR1 alterations. The phylogenic analysis revealed that the SLs developed independently from their main masses. It is possible that the main mass and its SLs were separated at an early stage in oncogenesis with shared FGFR1 alterations, and then they further expanded in different places. SLs of DNET are true tumors sharing pathogenic mutations with the main masses. It is plausible that multifocal tumor development takes place in the dysplastic cortex containing cells with a pathogenic genetic alteration. |
| first_indexed | 2024-04-09T22:57:58Z |
| format | Article |
| id | doaj.art-0483af31fb84405e8da30b835c451c3a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:57:58Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-0483af31fb84405e8da30b835c451c3a2023-03-22T11:08:09ZengNature PortfolioScientific Reports2045-23222023-01-011311910.1038/s41598-022-26636-7Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesionsYeajina Lee0Jeyul Yang1Seung Ah Choi2Seung‐Ki Kim3Sung-Hye Park4Hyun Joo Park5Jong-Il Kim6Ji Hoon Phi7Department of Biomedical Sciences, Seoul National University Graduate SchoolNeuro-Oncology Clinic, National Cancer CenterDivision of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of MedicineDivision of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of MedicineDepartment of Pathology, Seoul National University College of MedicineDepartment of Neurosurgery, Seoul National University College of MedicineDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDivision of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of MedicineAbstract Dysembryoplastic neuroepithelial tumor (DNET) is a low-grade brain tumor commonly associated with drug-resistant epilepsy. About half of DNETs are accompanied by tiny nodular lesions separated from the main mass. The existence of these satellite lesions (SLs) has shown a strong association with tumor recurrence, suggesting that they are true tumors. However, it is not known whether SLs represent multiple foci of progenitor tumor cell extension and migration or a multifocal development of the main DNET. This study was designed to elucidate the histopathology and pathogenesis of SLs in DNETs. Separate biopsies from the main masses and SLs with DNET were analyzed. We performed comparative lesion sequencing and phylogenetic analysis. FGFR1 K656E and K655I mutations or duplication of the tyrosine kinase domain was found in all 3 DNET patients and the main masses and their SLs shared the same FGFR1 alterations. The phylogenic analysis revealed that the SLs developed independently from their main masses. It is possible that the main mass and its SLs were separated at an early stage in oncogenesis with shared FGFR1 alterations, and then they further expanded in different places. SLs of DNET are true tumors sharing pathogenic mutations with the main masses. It is plausible that multifocal tumor development takes place in the dysplastic cortex containing cells with a pathogenic genetic alteration.https://doi.org/10.1038/s41598-022-26636-7 |
| spellingShingle | Yeajina Lee Jeyul Yang Seung Ah Choi Seung‐Ki Kim Sung-Hye Park Hyun Joo Park Jong-Il Kim Ji Hoon Phi Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions Scientific Reports |
| title | Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions |
| title_full | Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions |
| title_fullStr | Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions |
| title_full_unstemmed | Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions |
| title_short | Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions |
| title_sort | genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions |
| url | https://doi.org/10.1038/s41598-022-26636-7 |
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