Publications - Published papers

Please find below publications of our group. Currently, we list 500 papers. Some of the publications are in collaboration with the group of Sonja Prohaska and are also listed in the publication list for her individual group. Access to published papers (access) is restricted to our local network and chosen collaborators. If you have problems accessing electronic information, please let us know:

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The PCBP1 gene encoding poly(rC) binding protein I is recurrently mutated in Burkitt lymphoma.

Wagener, Rabea and Aukema, Sietse M. and Schlesner, Matthias and Haake, Andrea and Burkhardt, Birgit and Claviez, Alexander and Drexler, Hans G. and Hummel, Michael and Kreuz, Markus and Loeffler, Markus and Rosolowski, Maciej and L\'opez, Cristina and Möller, Peter and Richter, Julia and Rohde, Marius and Betts, Matthew J. and Russell, Robert B. and Bernhart, Stephan H. and Hoffmann, Steve and Rosenstiel, Philip and Schilhabel, Markus and Szczepanowski, Monika and Trümper, Lorenz and Klapper, Wolfram and Siebert, Reiner and ICGC MMML-Seq-Project, and ``Molecular Mechanisms in Malignant Lymphomas'' Network Project of the Deutsche Krebshilfe,

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PREPRINT 18-033:

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Genes, chromosomes \& cancer 54 (9): 555--564

Abstract


The genetic hallmark of Burkitt lymphoma is the translocation t(8;14)(q24;q32), or one of its light chain variants, resulting in IG-MYC juxtaposition. However, these translocations alone are insufficient to drive lymphomagenesis, which requires additional genetic changes for malignant transformation. Recent studies of Burkitt lymphoma using next generation sequencing approaches have identified various recurrently mutated genes including ID3, TCF3, CCND3, and TP53. Here, by using similar approaches, we show that PCBP1 is a recurrently mutated gene in Burkitt lymphoma. By whole-genome sequencing, we identified somatic mutations in PCBP1 in 3/17 (18\%) Burkitt lymphomas. We confirmed the recurrence of PCBP1 mutations by Sanger sequencing in an independent validation cohort, finding mutations in 3/28 (11\%) Burkitt lymphomas and in 6/16 (38\%) Burkitt lymphoma cell lines. PCBP1 is an intron-less gene encoding the 356 amino acid poly(rC) binding protein 1, which contains three K-Homology (KH) domains and two nuclear localization signals. The mutations predominantly (10/12, 83\%) affect the KH III domain, either by complete domain loss or amino acid changes. Thus, these changes are predicted to alter the various functions of PCBP1, including nuclear trafficking and pre-mRNA splicing. Remarkably, all six primary Burkitt lymphomas with a PCBP1 mutation expressed MUM1/IRF4, which is otherwise detected in around 20-40\% of Burkitt lymphomas. We conclude that PCBP1 mutations are recurrent in Burkitt lymphomas and might contribute, in cooperation with other mutations, to its pathogenesis.