Post‐transplant lymphoproliferative disorder subtypes correlate with different recurring chromosomal abnormalities

Djokic, Miroslav; Beau, Michelle M. Le; Swinnen, Lode J.; Smith, Sonali M.; Rubin, Charles M.; Anastasi, John; Carlson, Katrin M.

doi:10.1002/gcc.20287

Cited by 72 publications

(59 citation statements)

References 20 publications

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“…Genetically these lesions are monoclonal based both on immunoglobulin gene rearrangement studies and EBV Southern blot hybridization studies [23•, 24••]. Karyotyping has shown that only a small percentage of polymorphic PTLD cases (< 20%) have cytogenetic abnormalities [26,27].…”

Section: Polymorphicmentioning

confidence: 99%

Post-Transplantation Lymphoproliferative Disorders: Diagnosis, Prognosis, and Current Approaches to Therapy

et al. 2010

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Post-transplantation lymphoproliferative disorders (PTLD) are a heterogenous group of abnormal lymphoid proliferations that occur after solid organ transplant (SOT) or hematopoietic transplantation. PTLDs consist of a disease spectrum ranging from hyperplasia to aggressive lymphomas with 60-70% being Epstein-Barr virus positive. The majority of cases are B-cell, although 10-15% are of T-cell origin or rarely Hodgkin lymphoma. Recent SOT series suggest PTLD occurs at a median of 36-40 months after transplant. Clinically, extra-nodal disease is common (up to 75-85%) including CNS involvement, which is seen in 10-15% of all cases. Since the first report over 40 years ago, PTLD has remained one of the most morbid complications associated with SOT. However, recent data suggests improved survival in the modern era, especially with the integration of early rituximab-based therapy. These studies utilized first line rituximab (+/- chemotherapy) together with reduced immune suppression (RI) for monomorphic and polymorphic PTLD. It will be critical in future studies to determine which PTLDs are most amenable to initial therapy with RI alone, versus RI/rituximab, versus RI/rituximab/chemotherapy. Additionally, novel therapeutics, such as adoptive immunotherapy, should continue to be explored.

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Section: Polymorphicmentioning

confidence: 99%

Post-Transplantation Lymphoproliferative Disorders: Diagnosis, Prognosis, and Current Approaches to Therapy

et al. 2010

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“…The most frequent CNA was gain of 9p sequences detected in five cases (no. 10,13,15,17,20). The commonly gained region was localized at 9p24.1p24.3 Additionally examined with probes for JAK2 CDKNA2,and PDL1/PDL2, and optionally CEP 9.…”

Section: Clinicopathological Characteristicsmentioning

confidence: 99%

EBV-Positive and EBV-Negative Posttransplant Diffuse Large B Cell Lymphomas Have Distinct Genomic and Transcriptomic Features

Ferreiro

Morscio

Dierickx

et al. 2016

American Journal of Transplantation

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The molecular pathogenesis of posttransplant diffuse large B cell lymphoma (PT‐DLBCL) is largely unknown. We have recently shown that Epstein‐Barr virus–positive (EBV+) and –negative (EBV−) PT‐DLBCL have distinct gene expression profiles, and the transcriptomic profile of EBV− PT‐DLBCL is similar to that of DLBCL in immunocompetent individuals (IC‐DLBCL). To validate these observations at the genomic level, we performed array–comparative genome hybridization (aCGH) analysis of 21 EBV+ PT‐DLBCL, 6 EBV− PT‐DLBCL, and 11 control IC‐DLBCL, and subsequently combined genomic and transcriptomic data. The analysis showed that EBV+ and EBV− PT‐DLBCL have distinct aCGH profiles and shared only one recurrent imbalance. EBV− PT‐DLBCL, however, displayed at least 10 aberrations recurrent in IC‐DLBCL, among which characteristic gain of 3/3q and 18q, and loss of 6q23/TNFAIP3 as well as 9p21/CDKN2A. The most prevalent aberration in EBV+ PT‐DLBCL was gain/amplification of 9p24.1 targeting PDCD1LG2/PDL2. Our data indicate that the FOXP1 oncogene and the tumor suppressor CDKNA2 implicated in EBV− DLBCL, do not play a critical role in the pathogenesis of EBV+ PT‐DLBCL. Altogether, genomic profiling of PT‐/IC‐DLBCL confirms that EBV− and EBV+ PT‐DLBCL are distinct entities, while EBV− PT‐DLBCL has features in common with IC‐DLBCL. These findings support the hypothesis that EBV− PT‐DLBCL are de novo lymphomas in transplant recipients.

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“…Karyotype and comparative genomic hybridization studies reveal acquired gross chromosomal defects in about half of PTLD cases (42,149,156,195). Mutation or rearrangement of BCL6 (3q27), MYC (8q24), PAX5 (9p13), PIM1 (6p21), RHOH (4p13), or NRAS (1p13) may relate, at least in part, to somatic hypermutation occurring naturally in B cells (27,42,136,149,194,195). Methylation-induced inactivation of tumor suppressor genes (DAPK1 and MGMT) has also been described (24,35,159).…”

Section: Acquired Mutationsmentioning

confidence: 99%

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

2010

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SUMMARYEpstein-Barr virus (EBV) DNA measurement is being incorporated into routine medical practice to help diagnose, monitor, and predict posttransplant lymphoproliferative disorder (PTLD) in immunocompromised graft recipients. PTLD is an aggressive neoplasm that almost always harbors EBV DNA within the neoplastic lymphocytes, and it is often fatal if not recognized and treated promptly. Validated protocols, commercial reagents, and automated instruments facilitate implementation of EBV load assays by real-time PCR. When applied to either whole blood or plasma, EBV DNA levels reflect clinical status with respect to EBV-related neoplasia. While many healthy transplant recipients have low viral loads, high EBV loads are strongly associated with current or impending PTLD. Complementary laboratory assays as well as histopathologic examination of lesional tissue help in interpreting modest elevations in viral load. Circulating EBV levels in serial samples reflect changes in tumor burden and represent an effective, noninvasive tool for monitoring the efficacy of therapy. In high-risk patients, serial testing permits early clinical intervention to prevent progression toward frank PTLD. Restoring T cell immunity against EBV is a major strategy for overcoming PTLD, and novel EBV-directed therapies are being explored to thwart virus-driven neoplasia.

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Post‐transplant lymphoproliferative disorder subtypes correlate with different recurring chromosomal abnormalities

Cited by 72 publications

References 20 publications

Post-Transplantation Lymphoproliferative Disorders: Diagnosis, Prognosis, and Current Approaches to Therapy

Post-Transplantation Lymphoproliferative Disorders: Diagnosis, Prognosis, and Current Approaches to Therapy

EBV-Positive and EBV-Negative Posttransplant Diffuse Large B Cell Lymphomas Have Distinct Genomic and Transcriptomic Features

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

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