Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants.
Neuroblastoma (NBL), one of the main death-causing cancers in children, is known for its remarkable genetic heterogeneity and varied patient outcome spanning from spontaneous regression to widespread disease. Specific copy number variations and single gene rearrangements have been proven to be assoc...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0273280 |
| _version_ | 1811262331164819456 |
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| author | Weronika Przybyła Kirsti Marie Gjersvoll Paulsen Charitra Kumar Mishra Ståle Nygård Solveig Engebretsen Ellen Ruud Gunhild Trøen Klaus Beiske Lars Oliver Baumbusch |
| author_facet | Weronika Przybyła Kirsti Marie Gjersvoll Paulsen Charitra Kumar Mishra Ståle Nygård Solveig Engebretsen Ellen Ruud Gunhild Trøen Klaus Beiske Lars Oliver Baumbusch |
| author_sort | Weronika Przybyła |
| collection | DOAJ |
| description | Neuroblastoma (NBL), one of the main death-causing cancers in children, is known for its remarkable genetic heterogeneity and varied patient outcome spanning from spontaneous regression to widespread disease. Specific copy number variations and single gene rearrangements have been proven to be associated with biological behavior and prognosis; however, there is still an unmet need to enlarge the existing armamentarium of prognostic and therapeutic targets. We performed whole exome sequencing (WES) of samples from 18 primary tumors and six relapse samples originating from 18 NBL patients. Our cohort consists of 16 high-risk, one intermediate, and one very low risk patient. The obtained results confirmed known mutational hotspots in ALK and revealed other non-synonymous variants of NBL-related genes (TP53, DMD, ROS, LMO3, PRUNE2, ERBB3, and PHOX2B) and of genes cardinal for other cancers (KRAS, PIK3CA, and FLT3). Beyond, GOSeq analysis determined genes involved in biological adhesion, neurological cell-cell adhesion, JNK cascade, and immune response of cell surface signaling pathways. We were able to identify novel coding variants present in more than one patient in nine biologically relevant genes for NBL, including TMEM14B, TTN, FLG, RHBG, SHROOM3, UTRN, HLA-DRB1, OR6C68, and XIRP2. Our results may provide novel information about genes and signaling pathways relevant for the pathogenesis and clinical course in high-risk NBL. |
| first_indexed | 2024-04-12T19:23:23Z |
| format | Article |
| id | doaj.art-f0e9925e57f34ac398794c5ba94256b2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T19:23:23Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f0e9925e57f34ac398794c5ba94256b22022-12-22T03:19:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01178e027328010.1371/journal.pone.0273280Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants.Weronika PrzybyłaKirsti Marie Gjersvoll PaulsenCharitra Kumar MishraStåle NygårdSolveig EngebretsenEllen RuudGunhild TrøenKlaus BeiskeLars Oliver BaumbuschNeuroblastoma (NBL), one of the main death-causing cancers in children, is known for its remarkable genetic heterogeneity and varied patient outcome spanning from spontaneous regression to widespread disease. Specific copy number variations and single gene rearrangements have been proven to be associated with biological behavior and prognosis; however, there is still an unmet need to enlarge the existing armamentarium of prognostic and therapeutic targets. We performed whole exome sequencing (WES) of samples from 18 primary tumors and six relapse samples originating from 18 NBL patients. Our cohort consists of 16 high-risk, one intermediate, and one very low risk patient. The obtained results confirmed known mutational hotspots in ALK and revealed other non-synonymous variants of NBL-related genes (TP53, DMD, ROS, LMO3, PRUNE2, ERBB3, and PHOX2B) and of genes cardinal for other cancers (KRAS, PIK3CA, and FLT3). Beyond, GOSeq analysis determined genes involved in biological adhesion, neurological cell-cell adhesion, JNK cascade, and immune response of cell surface signaling pathways. We were able to identify novel coding variants present in more than one patient in nine biologically relevant genes for NBL, including TMEM14B, TTN, FLG, RHBG, SHROOM3, UTRN, HLA-DRB1, OR6C68, and XIRP2. Our results may provide novel information about genes and signaling pathways relevant for the pathogenesis and clinical course in high-risk NBL.https://doi.org/10.1371/journal.pone.0273280 |
| spellingShingle | Weronika Przybyła Kirsti Marie Gjersvoll Paulsen Charitra Kumar Mishra Ståle Nygård Solveig Engebretsen Ellen Ruud Gunhild Trøen Klaus Beiske Lars Oliver Baumbusch Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants. PLoS ONE |
| title | Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants. |
| title_full | Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants. |
| title_fullStr | Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants. |
| title_full_unstemmed | Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants. |
| title_short | Whole exome sequencing of high-risk neuroblastoma identifies novel non-synonymous variants. |
| title_sort | whole exome sequencing of high risk neuroblastoma identifies novel non synonymous variants |
| url | https://doi.org/10.1371/journal.pone.0273280 |
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