The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing
To decipher the mutational pattern of primary CNS lymphoma (PCNSL), we performed whole-exome sequencing to a median coverage of 103 × followed by mutation verification in 9 PCNSL and validation using Sanger sequencing in 22 PCNSL. We identified a median of 202 (range: 139-251) potentially somatic si...
Gespeichert in:
| Hauptverfasser: | , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2015
|
| In: |
Leukemia
Year: 2014, Jahrgang: 29, Heft: 3, Pages: 677-685 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2014.264 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/leu.2014.264 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/leu2014264 
|
| Verfasserangaben: | I. Vater, M. Montesinos-Rongen, M. Schlesner, A. Haake, F. Purschke, R. Sprute, N. Mettenmeyer, I. Nazzal, I. Nagel, J. Gutwein, J. Richter, I. Buchhalter, R.B. Russell, O.D. Wiestler, R. Eils, M. Deckert, and R. Siebert |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1713904551 | ||
| 003 | DE-627 | ||
| 005 | 20220818143517.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200708r20152014xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/leu.2014.264 |2 doi | |
| 035 | |a (DE-627)1713904551 | ||
| 035 | |a (DE-599)KXP1713904551 | ||
| 035 | |a (OCoLC)1341344898 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Vater, Inga |e VerfasserIn |0 (DE-588)1213367905 |0 (DE-627)1713906104 |4 aut | |
| 245 | 1 | 4 | |a The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing |c I. Vater, M. Montesinos-Rongen, M. Schlesner, A. Haake, F. Purschke, R. Sprute, N. Mettenmeyer, I. Nazzal, I. Nagel, J. Gutwein, J. Richter, I. Buchhalter, R.B. Russell, O.D. Wiestler, R. Eils, M. Deckert, and R. Siebert |
| 264 | 1 | |c 2015 | |
| 300 | |a 9 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Published: 05 September 2014 | ||
| 500 | |a Gesehen am 08.07.2020 | ||
| 520 | |a To decipher the mutational pattern of primary CNS lymphoma (PCNSL), we performed whole-exome sequencing to a median coverage of 103 × followed by mutation verification in 9 PCNSL and validation using Sanger sequencing in 22 PCNSL. We identified a median of 202 (range: 139-251) potentially somatic single nucleotide variants (SNV) and 14 small indels (range: 7-22) with potentially protein-changing features per PCNSL. Mutations affected the B-cell receptor, toll-like receptor, and NF-κB and genes involved in chromatin structure and modifications, cell-cycle regulation, and immune recognition. A median of 22.2% (range: 20.0-24.7%) of somatic SNVs in 9 PCNSL overlaps with the RGYW motif targeted by somatic hypermutation (SHM); a median of 7.9% (range: 6.2-12.6%) affects its hotspot position suggesting a major impact of SHM on PCNSL pathogenesis. In addition to the well-known targets of aberrant SHM (aSHM) (PIM1), our data suggest new targets of aSHM (KLHL14, OSBPL10, and SUSD2). Among the four most frequently mutated genes was ODZ4 showing protein-changing mutations in 4/9 PCNSL. Together with mutations affecting CSMD2, CSMD3, and PTPRD, these findings may suggest that alterations in genes having a role in CNS development may facilitate diffuse large B-cell lymphoma manifestation in the CNS. This may point to intriguing mechanisms of CNS tropism in PCNSL. | ||
| 534 | |c 2014 | ||
| 700 | 1 | |a Russell, Robert B. |e VerfasserIn |0 (DE-588)173751091 |0 (DE-627)698656334 |0 (DE-576)134591755 |4 aut | |
| 700 | 1 | |a Eils, Roland |d 1965- |e VerfasserIn |0 (DE-588)1020648287 |0 (DE-627)691291705 |0 (DE-576)361718195 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Leukemia |d London : Springer Nature, 1997 |g 29(2015), 3, Seite 677-685 |h Online-Ressource |w (DE-627)32046699X |w (DE-600)2008023-2 |w (DE-576)094139733 |x 1476-5551 |7 nnas |a The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing |
| 773 | 1 | 8 | |g volume:29 |g year:2015 |g number:3 |g pages:677-685 |g extent:9 |a The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing |
| 856 | 4 | 0 | |u https://doi.org/10.1038/leu.2014.264 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/leu2014264 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200708 | ||
| 993 | |a Article | ||
| 994 | |a 2015 | ||
| 998 | |g 1020648287 |a Eils, Roland |m 1020648287:Eils, Roland |d 160000 |d 160100 |e 160000PE1020648287 |e 160100PE1020648287 |k 0/160000/ |k 1/160000/160100/ |p 15 | ||
| 998 | |g 173751091 |a Russell, Robert B. |m 173751091:Russell, Robert B. |d 700000 |d 711000 |e 700000PR173751091 |e 711000PR173751091 |k 0/700000/ |k 1/700000/711000/ |p 13 | ||
| 999 | |a KXP-PPN1713904551 |e 3711341098 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"display":"Vater, Inga","role":"aut","family":"Vater","given":"Inga"},{"role":"aut","display":"Russell, Robert B.","given":"Robert B.","family":"Russell"},{"given":"Roland","family":"Eils","role":"aut","display":"Eils, Roland"}],"language":["eng"],"id":{"eki":["1713904551"],"doi":["10.1038/leu.2014.264"]},"type":{"bibl":"article-journal","media":"Online-Ressource"},"physDesc":[{"extent":"9 S."}],"relHost":[{"recId":"32046699X","origin":[{"publisherPlace":"London ; Basingstoke [u.a.] ; Basingstoke","dateIssuedKey":"1997","publisher":"Springer Nature ; Stockton Press ; Nature Publ. Group","dateIssuedDisp":"1997-"}],"part":{"text":"29(2015), 3, Seite 677-685","issue":"3","pages":"677-685","year":"2015","extent":"9","volume":"29"},"pubHistory":["Nachgewiesen 11.1997 -"],"type":{"bibl":"periodical","media":"Online-Ressource"},"id":{"zdb":["2008023-2"],"issn":["1476-5551"],"eki":["32046699X"]},"note":["Gesehen am 15.03.04"],"disp":"The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencingLeukemia","language":["eng"],"title":[{"title_sort":"Leukemia","subtitle":"normal and malignant hemopoiesis ; a peer-reviewed journal","title":"Leukemia"}],"physDesc":[{"extent":"Online-Ressource"}]}],"title":[{"title_sort":"mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing","title":"The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing"}],"recId":"1713904551","name":{"displayForm":["I. Vater, M. Montesinos-Rongen, M. Schlesner, A. Haake, F. Purschke, R. Sprute, N. Mettenmeyer, I. Nazzal, I. Nagel, J. Gutwein, J. Richter, I. Buchhalter, R.B. Russell, O.D. Wiestler, R. Eils, M. Deckert, and R. Siebert"]},"note":["Published: 05 September 2014","Gesehen am 08.07.2020"],"origin":[{"dateIssuedKey":"2015","dateIssuedDisp":"2015"}]} | ||
| SRT | |a VATERINGARMUTATIONAL2015 | ||