The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing

• Verfasst von: Vater, Inga [VerfasserIn]
• Verfasst von: Russell, Robert B. [VerfasserIn]
• Verfasst von: Eils, Roland [VerfasserIn]
• Titel: The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing
• Verf.angabe: 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
• Jahr: 2015
• Jahr des Originals: 2014
• Umfang: 9 S.
• Fussnoten: Published: 05 September 2014 ; Gesehen am 08.07.2020
• Titel Quelle: Enthalten in: Leukemia
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2015
• Band/Heft Quelle: 29(2015), 3, Seite 677-685
• ISSN Quelle: 1476-5551
• DOI: doi:10.1038/leu.2014.264
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1713904551

Abstract

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.