Epstein-Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances.
View Article and Find Full Text PDFDiamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia, underlied by haploinsufficient mutations in genes coding for ribosomal proteins (RP) in approximately 70% of cases. DBA is frequently associated with somatic malformations, endocrine dysfunction and with an increased predisposition to cancer. Here we present clinical and genetic characteristics of 62 patients from 52 families enrolled in the Czech and Slovak DBA Registry.
View Article and Find Full Text PDFObjectives: A complex karyotype (CK) is considered a poor prognostic marker in chronic lymphocytic leukemia (CLL).
Methods: The study analyzed 644 untreated CLL patients (pts) using conventional/molecular cytogenetics to reveal the presence of a CK and its composition and to assess its predictive value. The mutational status ofTP53 was detected by next generation sequencing.
Background: Better risk-stratification of patients with chronic lymphocytic leukemia (CLL) and identification of subsets of ultra-high-risk (HR)-CLL patients are crucial in the contemporary era of an expanded therapeutic armamentarium for CLL.
Methods: A multivariate patient similarity network and clustering was applied to assess the prognostic values of routine genetic, laboratory, and clinical factors and to identify subsets of ultra-HR-CLL patients. The study cohort consisted of 116 HR-CLL patients (F/M 36/80, median age 63 yrs) carrying del(11q), del(17p)/TP53 mutations and/or complex karyotype (CK) at the time of diagnosis.
Clin Lymphoma Myeloma Leuk
November 2018
Background: TP53 mutation (TP53mut) and a complex karyotype (CK) were shown to be predictors of poor outcome in mantle-cell lymphoma (MCL). In this study we examined the combined effect of both of these risk factors.
Patients And Methods: Patients diagnosed with MCL between January 2000 and December 2014 (n = 74) were evaluated.
Here we report a C-terminal RUNX1 mutation in a family with platelet disorder and predisposition to myeloid malignancies. We identified the mutation c.866delG:p.
View Article and Find Full Text PDFBiomed Pap Med Fac Univ Palacky Olomouc Czech Repub
March 2018
Objective: Prophylaxis of iodine deficiency-related disorders with iodized salt in Slovakia was introduced in 1951. This prophylactic measure yielded remarkably good results. Endemic goiter and endemic cretinism disappeared.
View Article and Find Full Text PDFHepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six i(7)(q10)-positive HSTL cases, including HSTL-derived cell line (DERL-2), and three cases with ring 7 [r(7)], the recently identified rare variant aberration. Using high resolution array CGH, we profiled all cases and mapped the common deleted region (CDR) at 7p22.
View Article and Find Full Text PDFThe simultaneous occurrence of polycythemia vera (PV) and chronic lymphocytic leukemia (CLL) is a rare event that offers a possibility to study their common origin. PV originates from self-renewing hematopoietic stem cells (HSC) with both lymphoid and myeloid potential(–3). It has been reported that CLL also originates from self-renewing HSC with a potential for both lymphoid and myeloid differentiation(4, 5).
View Article and Find Full Text PDFBiomed Pap Med Fac Univ Palacky Olomouc Czech Repub
April 2015
Aims: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia with a very heterogeneous course. Progress in molecular genetic characterization of CLL has confirmed the prognostic role of unbalanced chromosomal abnormalities currently defined by molecular cytogenetic methods: conventional karyotyping and FISH. However, a significant percentage of genomic abnormalities escapes routine investigation due to the limitations of these methods.
View Article and Find Full Text PDFThe genetic background of mature B-cell neoplasms with villous lymphocytes is poorly understood. We identified a novel breakpoint region at 14q32.13 that was rearranged together with IGH/14q32.
View Article and Find Full Text PDFGenetic events underlying pathogenesis of nodal and extranodal marginal zone lymphoma are not completely understood. We report here a novel t(X;14)(p11.4;q32.
View Article and Find Full Text PDFArray-based comparative genomic hybridization (arrayCGH) studies in chronic lymphocytic leukemia (CLL) have revealed novel recurrent chromosomal imbalances, such as a gain of chromosome 2p. However, a detailed cytogenetic analysis of the 2p gain region has not been elucidated. Here, we present cytogenetic and molecular cytogenetic analysis of 16 such cases selected from a group of 200 patients with CLL based on CGH and/or arrayCGH data.
View Article and Find Full Text PDFLeukemias/lymphomas with IGH-involving del(14q)(1) commonly lose the DLK1-GTL2 imprinted domain that comprises several paternally and maternally expressed genes, including a cluster of microRNAs. Given that deletion of this region could lead to inactivation of a monoallelically expressed tumor suppressor gene, our study aimed at determination of the parental origin of del(14q/IGH). The designed allele-specific methylation study of the DLK1/GTL2 intergenic differentially methylated region allowed us to determine the parental origin of del(14q/IGH) in 9/20 analyzed cases.
View Article and Find Full Text PDFHepatoblastoma is the most common primary hepatic tumor in children, and only a limited number of detailed karyotypic analyses have been reported to date. In the present study, cytogenetic abnormalities were identified in nine cases of hepatoblastoma from a single institution. Among characteristic chromosomal changes detected were simple numerical aberrations, structural alterations of chromosomes 1, 2, and 8, and the recurrent unbalanced rearrangements der(4)t(1;4)(q25.
View Article and Find Full Text PDFAbnormalities of chromosome 1 are among the most frequent chromosomal aberrations in patients with multiple myeloma (MM) and are considered a poor-risk genetic feature. To define the frequency and minimal region of 1q gain, we performed immunophenotyping and fluorescence in situ hybridization, comparative genomic hybridization (CGH), and array-CGH in 30 patients in relapse and progression of MM. Gain of 1q21 was found in 15 patients (50%), and in 14 of them whole-arm gain was found.
View Article and Find Full Text PDFBackground: We present the results of a cytogenetic and molecular cytogenetic analysis of a series of patients with bone and soft tissue tumors. PATIENTS ANDMETHODS: We analyzed a cohort of 26 patients with Ewing sarcoma/PNET, 15 patients with rhabdomyosarcoma, 5 with synovial sarcoma and one patient with an undifferentiated sarcoma using the cytogenetic and molecular cytogenetic techniques M-FISH and arrayCGH.
Results: We found nonrandom chromosomal structural and numerical changes with diagnostic and prognostic relevance in most patients.
On example of three patients with septo-optic dysplasia the authors present a rare clinical entity involving combined disturbances of endocrine and neurologic systems and variable expressed clinical triad: 1) pituitary aplasia/dysplasia with pituitary hormones deficiency, 2) developmental disturbance of the middle-brain structures (corpus callosum and septum pellucidum), and 3) dysplastic changes of the optic nerve. The knowledge about components belonging to the competence of other specialists and awareness of consequences of untreated hypopituitarism, are imperatives for interdisciplinary cooperation of ophthalmologist, neurologist, radiologist, and endocrinologist. Moreover, they predict early initiation of the adequate and often vital therapy.
View Article and Find Full Text PDFReported here are 72 previously treated Philadelphia chromosome-positive (Ph+) CML patients on imatinib (IM) therapy, with a focus on patients with additional chromosomal aberrations (CAs). At the start of IM treatment, 49 patients exhibited only the Ph chromosome (68%) and 23 patients (32%) had one or more additional CAs. The most frequent additional changes were deletions on the der(9q) (8 of 23), trisomy 8 (3 of 23), and an extra copy of the Ph chromosome (2 of 23).
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