Relapsed diffuse large B-cell lymphoma present different genomic profiles between early and late relapses
نویسندگان
چکیده
Despite major advances in first-line treatment, a significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) will experience treatment failure. Prognosis is particularly poor for relapses occurring less than one year after the end of first-line treatment (early relapses/ER) compared to those occurring more than one year after (late relapses/LR). To better understand genomic alterations underlying the delay of relapse, we identified copy number variations (CNVs) on 39 tumor samples from a homogeneous series of patients included in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) prospective study. To identify CNVs associated with ER or LR, we devised an original method based on Significance Analysis of Microarrays, a permutation-based method which allows control of false positives due to multiple testing. Deletions of CDKN2A/B (28%) and IBTK (23%) were frequent events in relapsed DLBCLs. We identified 56 protein-coding genes and 25 long non-coding RNAs with significantly differential CNVs distribution between ER and LR DLBCLs, with a false discovery rate < 0.05. In ER DLBCLs, CNVs were related to transcription regulation, cell cycle and apoptosis, with duplications of histone H1T (31%), deletions of DIABLO (26%), PTMS (21%) and CK2B (15%). In LR DLBCLs, CNVs were related to immune response, with deletions of B2M (20%) and CD58 (10%), cell proliferation regulation, with duplications of HES1 (25%) and DVL3 (20%), and transcription regulation, with MTERF4 deletions (20%). This study provides new insights into the genetic aberrations in relapsed DLBCLs and suggest pathway-targeted therapies in ER and LR DLBCLs.
منابع مشابه
miR-4284 and miR-4484 as Putative Biomarkers for Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. MicroRNAs (miRNAs) are endogenous small RNA, which can regulate gene expression at the post-transcriptional level. MiRNA profiling has shown a great potential as novel diagnostic and prognostic biomarkers. The present study was performed at the Nemazee Teaching Hospital (Shiraz, Iran) from 2011 to 2013.The aim of thi...
متن کاملEarly detection of intravascular large B-cell lymphoma by 18FDG-PET/CT with diffuse FDG uptake in the lung without respiratory symptoms or chest CT abnormalities
Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of systemic extranodal non-Hodgkin diffuse large B-cell lymphoma (DLBCL). We report a rare case of IVLBCL who showed diffuse 18F-fluorodeoxyglucose (FDG) uptake in the lung in FDG-positron emission tomography/computed tomography (PET/CT) without respiratory symptoms or chest CT abnormalities. Serum biochemical studies...
متن کاملGenetic background and evolution of relapses in aggressive B-cell lymphomas
Relapses of aggressive B-cell lymphomas pose a higher risk to affected patients because of potential treatment resistance and usually rapid tumor growth. Recent advances, such as targeting Bruton tyrosine kinase, have provided promising results in small numbers of cases, but treatment for the majority of patients remains challenging and outcomes are generally poor. A number of recent studies ha...
متن کاملHISTIOCYTE-RICH B-CELL LYMPHOMA: A CASE REPORT OF A RARE VARIANT OF DIFFUSE LARGE B-CELL LYMPHOMA
The authors describe a case of histiocyte-rich B-cell lymphoma (HR-BCL), a variant of diffuse large B-cell lymphoma, in a 51-year-old man. The patient presented with large axillary lymphadenopathy. Histopathologic and immunohistochemical examination of lymph node biopsy revealed diffuse effacement of the lymph node architecture by reactive histiocytes and neoplastic CD20 positive B cells. ...
متن کاملThe Evaluation of Immunophenotypes in Diffuse Large B Cell Lymphoma: A Single Center Study
Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of mature B lymphocytes. It is known as a heterogeneous disease with variable therapeutic responses and alternative therapies. Morphological and immunophenotypical evaluation of the biopsy specimens can help diagnose DLBCL. Methods: In the current study, 44 patients were chosen from Shaheed Sadoghi Hospital (2010&nda...
متن کامل