Clonality and evolutionary history of rhabdomyosarcoma.
To infer the subclonality of rhabdomyosarcoma (RMS) and predict the temporal order of genetic events for the tumorigenic process, and to identify novel drivers, we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal RMS pairs using deep whole-genom...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-03-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4358975?pdf=render |
| _version_ | 1829118119123091456 |
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| author | Li Chen Jack F Shern Jun S Wei Marielle E Yohe Young K Song Laura Hurd Hongling Liao Daniel Catchpoole Stephen X Skapek Frederic G Barr Douglas S Hawkins Javed Khan |
| author_facet | Li Chen Jack F Shern Jun S Wei Marielle E Yohe Young K Song Laura Hurd Hongling Liao Daniel Catchpoole Stephen X Skapek Frederic G Barr Douglas S Hawkins Javed Khan |
| author_sort | Li Chen |
| collection | DOAJ |
| description | To infer the subclonality of rhabdomyosarcoma (RMS) and predict the temporal order of genetic events for the tumorigenic process, and to identify novel drivers, we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal RMS pairs using deep whole-genome sequencing. Intriguingly, we find that loss of heterozygosity of 11p15.5 and mutations in RAS pathway genes occur early in the evolutionary history of the PAX-fusion-negative-RMS (PFN-RMS) subtype. We discover several early mutations in non-RAS mutated samples and predict them to be drivers in PFN-RMS including recurrent mutation of PKN1. In contrast, we find that PAX-fusion-positive (PFP) subtype tumors have undergone whole-genome duplication in the late stage of cancer evolutionary history and have acquired fewer mutations and subclones than PFN-RMS. Moreover we predict that the PAX3-FOXO1 fusion event occurs earlier than the whole genome duplication. Our findings provide information critical to the understanding of tumorigenesis of RMS. |
| first_indexed | 2024-12-13T10:14:41Z |
| format | Article |
| id | doaj.art-df4d2ffc7ee84072a7cc3f1788b039bb |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-13T10:14:41Z |
| publishDate | 2015-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-df4d2ffc7ee84072a7cc3f1788b039bb2022-12-21T23:51:21ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-03-01113e100507510.1371/journal.pgen.1005075Clonality and evolutionary history of rhabdomyosarcoma.Li ChenJack F ShernJun S WeiMarielle E YoheYoung K SongLaura HurdHongling LiaoDaniel CatchpooleStephen X SkapekFrederic G BarrDouglas S HawkinsJaved KhanTo infer the subclonality of rhabdomyosarcoma (RMS) and predict the temporal order of genetic events for the tumorigenic process, and to identify novel drivers, we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal RMS pairs using deep whole-genome sequencing. Intriguingly, we find that loss of heterozygosity of 11p15.5 and mutations in RAS pathway genes occur early in the evolutionary history of the PAX-fusion-negative-RMS (PFN-RMS) subtype. We discover several early mutations in non-RAS mutated samples and predict them to be drivers in PFN-RMS including recurrent mutation of PKN1. In contrast, we find that PAX-fusion-positive (PFP) subtype tumors have undergone whole-genome duplication in the late stage of cancer evolutionary history and have acquired fewer mutations and subclones than PFN-RMS. Moreover we predict that the PAX3-FOXO1 fusion event occurs earlier than the whole genome duplication. Our findings provide information critical to the understanding of tumorigenesis of RMS.http://europepmc.org/articles/PMC4358975?pdf=render |
| spellingShingle | Li Chen Jack F Shern Jun S Wei Marielle E Yohe Young K Song Laura Hurd Hongling Liao Daniel Catchpoole Stephen X Skapek Frederic G Barr Douglas S Hawkins Javed Khan Clonality and evolutionary history of rhabdomyosarcoma. PLoS Genetics |
| title | Clonality and evolutionary history of rhabdomyosarcoma. |
| title_full | Clonality and evolutionary history of rhabdomyosarcoma. |
| title_fullStr | Clonality and evolutionary history of rhabdomyosarcoma. |
| title_full_unstemmed | Clonality and evolutionary history of rhabdomyosarcoma. |
| title_short | Clonality and evolutionary history of rhabdomyosarcoma. |
| title_sort | clonality and evolutionary history of rhabdomyosarcoma |
| url | http://europepmc.org/articles/PMC4358975?pdf=render |
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