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.
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http://dx.doi.org/10.1002/gcc.22268 | DOI Listing |
Blood Adv
January 2025
Simon Fraser University, Burnaby, British Columbia, Canada.
Comprehensive genetic analysis of tumors with exome or whole genome sequencing has enabled the identification of the genes that are recurrently mutated in cancer. This has stimulated a series of exciting advances over the past 15 years, guiding us to new molecular biomarkers and therapeutic targets among the common mature B-cell neoplasms. In particular, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt lymphoma (BL) have each been the subject of considerable attention in this field.
View Article and Find Full Text PDFDent J (Basel)
December 2024
Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens (NKUA), Greece 2 Thivon Street, 11527 Athens, Greece.
Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma (NHL), subdivided into endemic, sporadic, and immunodeficiency-associated forms. While jaw lesions are common in endemic BL, they are infrequent in sporadic cases, only rarely constituting the first manifestation of the disease. The aim of this study is to present a rare pediatric case of sporadic BL first manifesting as gingival swellings and tooth hypermobility and provide a review of all the published sporadic BL case reports as the first sign of disease.
View Article and Find Full Text PDFSAGE Open Med
January 2025
Department of Pathology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Background: To investigate the trends in Burkitt lymphoma incidence, mortality, and disability-adjusted life-years, considering sex and age, from 1990 to 2021, with a 20-year forecast.
Method: Data regarding Burkitt lymphoma were extracted from the Global Burden of Disease study for the year 2021.
Results: Globally, there were 19,072 incident cases of Burkitt lymphoma in 2021.
Genes Chromosomes Cancer
January 2025
Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany.
Mature aggressive B-cell lymphomas, such as Burkitt lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL), show variations in microRNA (miRNA) expression. The entity of High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) shares several biological features with both BL and DLBCL but data on its miRNA expression profile are yet scarce. Hence, this study aims to analyze the potential differences in miRNA expression of HGBCL-11q compared to BL and DLBCL.
View Article and Find Full Text PDFTransl Pediatr
December 2024
Department of Hematology, Chongqing Medical University Affiliated Children's Hospital, Chongqing, China.
Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication that can arise following solid organ transplantation or hematopoietic stem cell transplantation. It encompasses a spectrum of lymphoproliferative lesions, ranging from benign reactive hyperplasia to malignant tumors, and is among the most severe complications following liver transplantation in children. It is essential for clinicians to gain a comprehensive understanding of the prevention, clinical manifestations, early diagnosis, and treatment strategies for PTLD in order to reduce mortality rates.
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