Genomic characterization of primary central nervous system lymphoma

Abstract Primary central nervous system lymphoma (PCNSL) is a rare malignancy confined to the central nervous system (CNS), and majority of PCNSL is pathologically classified as diffuse large B-cell lymphoma (DLBCL). We have now performed whole-exome sequencing for 41 tumor tissues of DLBCL-type PCNSL and paired normal specimens and also RNA-sequencing for 30 tumors, revealing a very high frequency of nonsynonymous somatic mutations in PIM1 (100 %), BTG2 (92.7 %), and MYD88 (85.4 %). Many genes in the NF-κB pathway are concurrently mutated within the same tumors. Further, focal deletion or somatic mutations in the HLA genes are associated with poor prognosis. Copy number amplification and overexpression of genes at chromosome 7q35 were both found to predict short progression-free survival as well. Oncogenic mutations in GRB2 were also detected, the effects of which in cultured cells were attenuated by inhibitors of the downstream kinases MAP2K1 and MAP2K2. Individuals with tumors positive for MYD88 mutations also harbored the same mutations at a low frequency in peripheral blood mononuclear cells, suggesting that MYD88 mutation-positive precancerous cells originate outside of the CNS and develop into lymphoma after additional genetic hits that confer adaptation to the CNS environment.
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Authors: Furst T, Hoffman H, Chin LS Abstract BACKGROUND: Recent primary central nervous system lymphoma (PCNSL) literature indicates that younger patients benefit from improved survival, however, this benefit is not shared by those 70+ years of age. The purpose of this study is to examine mortality trends in PCNSL patients 70+ years of age to better understand why improved prognosis has not yet reached this rapidly growing population subset. METHODS: 2075 cases (1973-2012, age at diagnosis 70+ years) within the Surveillance, Epidemiology, and End Results (SEER) database were included in Kaplan-Meier and multiv...
Source: Journal of Neurosurgical Sciences - Category: Neurosurgery Tags: J Neurosurg Sci Source Type: research
Authors: Seidel S, Schlegel U Abstract Introduction: Primary CNS lymphomas (PCNSL) are highly aggressive tumors and optimal treatment is not yet defined. For the last two decades clinical trials have focused on developing efficient chemotherapy protocols with or without dose reduced radiation to avoid late cognitive decline after whole brain radiotherapy (WBRT). Areas covered: This review addresses the question if these substantial developments have led to clinically relevant therapeutic improvement for PCNSL within the last decade. Expert opinion: The high risk of neurotoxic side effects of WBRT was further substa...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
Condition:   Primary Central Nervous System Lymphoma Interventions:   Drug: Methotrexate;   Drug: Rituximab;   Drug: Lenalidomide Sponsors:   Peking Union Medical College Hospital;   Beijing Tiantan Hospital;   Xuanwu Hospital, Beijing;   Peking University Third Hospital;   Beijing Hospital;   Peking University First Hospital;   Chinese PLA General Hospital Recruiting
Source: - Category: Research Source Type: clinical trials
Colen Morón The ability to non-invasively predict outcomes and monitor treatment response in primary central nervous system lymphoma (PCNSL) is important as treatment regimens are constantly being trialed. The aim of this study was to assess the validity of using apparent diffusion coefficient (ADC) histogram values to predict Ki-67 expression, a tumor proliferation marker, and patient outcomes in PCNSL in both immunocompetent patients and patients living with HIV (PLWH). Qualitative PCNSL magnetic resonance imaging (MRI) characteristics from 93 patients (23 PLWH and 70 immunocompetent) were analyzed, and who...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This article provides a brief discussion of the major 2016 updates to the WHO CNS classification scheme and reviews typical MR imaging findings of adult primary CNS neoplasms, including diffuse infiltrating gliomas, ependymal tumors, neuronal/glioneuronal tumors, pineal gland tumors, meningiomas, nerve sheath tumors, solitary fibrous tumors, and lymphoma. PMID: 31582041 [PubMed - in process]
Source: Radiologic Clinics of North America - Category: Radiology Authors: Tags: Radiol Clin North Am Source Type: research
Contributors : Reiner Siebert ; Julia VogtSeries Type : Methylation profiling by genome tiling array ; Third-party reanalysisOrganism : Homo sapiensGenome wide DNA methylation profiling of 26 primary central nervous system lymphomas (PCNSL). The Illumina Infinium HumanMethylation 450 BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in PCNSL samples.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by genome tiling array Third-party reanalysis Homo sapiens Source Type: research
ConclusionsThe compromised immune status in na ïve-pts may explain their worst NHL conditions at diagnosis and toxicity during chtp. The immediate start of HAART in combination with chemotherapy probably reduce the impact of these factors in term of response to treatment and survival (RR, PFS and OS). CD4+ count together with HAART remain the i ndependent prognostic factor with the greatest influence on OS [exp vs naïve-pts: OS HR 0.83 (95% CI); OS/CD4+ HR 1.80 (95% CI)]. Naive-pts should be treated with standard chtp regimens, without modification of dose or schedule.Legal entity responsible for the studyASST-FB...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsTexture analysis has potential in the differentiation between primary central nervous system lymphoma from metastatic brain tumors. Moreover, combination of single texture shows more promising and effective ability in discrimination.Legal entity responsible for the studyXuelei Ma.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsMYD88 L265P real-time PCR could be a good diagnostic tool for the patients with VRL harboring MYD88 L265P mutation. We concluded that exome or gene panel testing of VRL and confirmation of the presence of a number of somatic mutation and mutation profile may facilitate the diagnosis of VRL in a subset of patients.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive type of extranodal non-Hodgkin lymphoma that carries an unsatisfactory prognosis. Treating refractory PCNSL is challenging because of resistance to conventional cytotoxic and intrathecal chemotherapies. Therefore, novel therapeutic approaches are needed. Here, we report a 12-year-old boy with CD20-positive PCNSL, which was refractory to combination chemotherapy and intravenous rituximab. However, the patient achieved complete remission after repeated intraventricular rituximab administration. The results of this case indicate that intraventricular rit...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Clinical and Laboratory Observations Source Type: research
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