Whole-Exome Sequencing Revealed the Mutational Profiles of Primary Central Nervous System Lymphoma |
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| Institution: | 1. Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China;2. Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi''an, China;3. Department of Neurosurgery, the Sixth Medical Centre, Chinese PLA General Hospital, Beijing,China;1. Institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Faculty of Medicine, Tel Aviv University, Israel;2. Hematology Division, Sheba Medical Center, Faculty of Medicine, Tel Aviv University, Israel;1. Tumor-Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg;2. Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;3. PERSIMUNE, Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark;4. Center of Oncology and Hematology, Hospital Santa Lúcia Sul, Brasilia, Brazil;5. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;1. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA;2. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;3. Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL;1. Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, India;2. Department of Medical Oncology, Dayanand Medical College and Hospital, Ludhiana, India;3. Neuberg Supratech Reference Laboratories, Ahmedabad, India;4. Department of Hematopathology, All India Institute of Medical Sciences, New Delhi, India;5. Department of Molecular Genetics, Dayanand Medical College and Hospital, Ludhiana, India;6. Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, India |
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| Abstract: | BackgroundPrimary central nervous system lymphoma (PCNSL) is a highly aggressive type of extranodal non-Hodgkin lymphoma, of which approximately 90% of the cases are diffuse large B-cell lymphoma (DLBCL). In recent years, the incidence of PCNSL has significantly increased in women and older men. Although advanced treatments such as high-dose methotrexate (HD-MTX) and targeted agents have been introduced, the prognosis of these patients remains poorer than those with other forms of non-Hodgkin's lymphoma.MethodsTwelve cases of Chinese PCNSL were analyzed to detect their genetic alterations using whole-exome sequencing (WES). We identified 448 potential somatic single nucleotide variants (SNVs) with a median of 12 SNVs per PCNSL sample and 35 small indels with potentially protein-changing features in 9 PCNSL samples.ResultsWe found that myeloid differentiation factor 88 (MYD88) had the highest mutation frequency, which affected the activity of the nuclear factor-κB (NF-κB) pathway. PCNSL samples with low-density lipoprotein receptor-related protein 1B (LRP1B) mutations had a higher mutation rate than samples with wild-type LRP1B. Polycystic kidney and hepatic disease 1 (PKHD1), the causal gene of autosomal recessive polycystic kidney disease (ARPKD), was identified in 2 PCNSL cases and exhibited missense mutations. Pathway analysis revealed enrichment in pathways associated with central carbon metabolism in cancer, renal cell carcinoma, nicotine addiction, bladder cancer, and long-term depression.ConclusionsWES revealed significantly mutated genes associated with the molecular mechanisms of PCNSL, which could serve as therapeutic targets to improve patient outcomes. |
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| Keywords: | Genetic alteration Pathway analysis Interaction network |
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