Cohesin RAD21 Gene Promoter Methylation in Patients with Chronic Lymphocytic Leukemia

2018 ◽  
Vol 154 (3) ◽  
pp. 126-131 ◽  
Author(s):  
Agapi Ioannidou ◽  
Sophia Zachaki ◽  
Maria Karakosta ◽  
Aggeliki Daraki ◽  
Paraskevi Roussou ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Promoter Methylation ◽  
Chromosomal Abnormalities ◽  
Methylation Status ◽  
Cpg Islands ◽  
Gene Promoter ◽  
Common Type ◽  
Lymphocytic Leukemia ◽  
Cytogenetic Abnormalities ◽  
Epigenetic Processes

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults and is characterized by the presence of specific cytogenetic abnormalities. CLL research has been focused on epigenetic processes like gene promoter methylation of CpG islands. In the present study, the methylation status of the RAD21 gene is studied and associated with cytogenetic findings in CLL patients in order to investigate its possible implication in CLL pathogenesis and the formation of CLL chromosomal abnormalities.

scholarly journals Impact Of TP53 Gene Promoter Methylation On Chronic Lymphocytic Leukemia Pathogenesis And Progression

2019 ◽  
Vol Volume 10 ◽  
pp. 399-404
Author(s):  
Waleed Haji Saeed ◽  
Adil Abozaid Eissa ◽  
Adnan Anwar Al-Doski
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Promoter Methylation ◽  
Gene Promoter ◽  
Tp53 Gene ◽  
Lymphocytic Leukemia

Abstract 36: FCGR2A Promoter Methylation and Risks for IVIG Unresponsiveness in Kawasaki Disease

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Ho-Chang Kuo ◽  
Kai-Sheng Hsieh ◽  
Wei-Chiao Chang ◽  
Keyword(s):  
Kawasaki Disease ◽  
Promoter Methylation ◽  
Systemic Vasculitis ◽  
Methylation Status ◽  
Cpg Islands ◽  
Gene Promoter ◽  
Ivig Therapy ◽  
Ivig Treatment ◽  
Fc Fragment ◽  
Cpg Sites

Kawasaki disease (KD) is characterized by pediatric systemic vasculitis of an unknown cause and the Fc Fragment of IgG, Low Affinity IIa, Receptor ( FCGR2A ) gene was reported to involve in increasing susceptibility of KD. Because DNA methylation is one of the epigenetic mechanisms that control gene expression, we hypothesized that methylation status of CpG islands in FCGR2A promoter predisposes an individual to Kawasaki disease. We recruited 36 KD patients and 24 healthy subjects with informed consents. And eleven potential methylation loci within the targeted promoter region (chr1:161474603-161475102) of Fc Fragment of IgG, Low Affinity IIa, Receptor were selected for investigation. Methylation at the CpG sites G, H and J displayed a strongly associations with KD, whereas CpG sites B,C,E,F,H,J and K were found to be correlated with non-responsive to IVIG treatment. In addition, CpG sites G, J and K were predicted as the significant transcription factor binding site for NF-kB, Myc-Max and SP2 respectively. Our study reports a significant association between the promoter methylation of FCGR2A , susceptibility of Kawasaki disease and therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter may be an important marker for optimizing IVIG therapy.

Prospective Evaluation of Clonal Evolution During Long-Term Follow-Up of Patients With Untreated Early-Stage Chronic Lymphocytic Leukemia

2006 ◽  
Vol 24 (28) ◽  
pp. 4634-4641 ◽  
Author(s):  
Tait D. Shanafelt ◽  
Thomas E. Witzig ◽  
Stephanie R. Fink ◽  
Robert B. Jenkins ◽  
Sarah F. Paternoster ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Chromosomal Abnormalities ◽  
Early Stage ◽  
Clonal Evolution ◽  
Prospective Trial ◽  
Lymphocytic Leukemia ◽  
Cytogenetic Abnormalities ◽  
Long Term Follow Up

Purpose Retrospective studies suggest cytogenetic abnormalities detected by interphase fluorescent in situ hybridization (FISH) can identify patients with chronic lymphocytic leukemia (CLL) who will experience a more aggressive disease course. Other studies suggest that patients may acquire chromosome abnormalities during the course of their disease. There are minimal prospective data on the clinical utility of the widely used hierarchical FISH prognostic categories in patients with newly diagnosed early-stage CLL or the frequency of clonal evolution as determined by interphase FISH. Patients and Methods Between 1994 and 2002, we enrolled 159 patients with previously untreated CLL (83% Rai stage 0/I) on a prospective trial evaluating clonal evolution by FISH. Patients provided baseline and follow-up specimens for FISH testing during 2 to 12 years. Results Chromosomal abnormalities detected by FISH at study entry predicted overall survival. Eighteen patients experienced clonal evolution during follow-up. The rate of clonal evolution increased with duration of follow-up with only one occurrence in the first 2 years (n = 71; 1.4%) but 17 occurrences (n = 63; 27%) among patients tested after 5+ years. Clonal evolution occurred among 10% of ZAP-70–negative and 42% of ZAP-70–positive patients at 5+ years (P = .008). Conclusion This clinical trial confirms prospectively that cytogenetic abnormalities detected by FISH can predict overall survival for CLL patients at the time of diagnosis, but also suggests that many patients acquire new abnormalities during the course of their disease. Patients with higher ZAP-70 expression may be more likely to experience such clonal evolution. These findings have important implications for both clinical management and trials of early treatment for patients with high-risk, early-stage CLL.

Promoter Methylation Status in Pro-opiomelanocortin Does Not Contribute to Dyspigmentation in Hypertrophic Scar

2019 ◽  
Author(s):  
Bonnie C Carney ◽  
Ryan D Dougherty ◽  
Lauren T Moffatt ◽  
Cynthia M Simbulan-Rosenthal ◽  
Jeffrey W Shupp ◽  
...  
Keyword(s):  
Protein Expression ◽  
Promoter Methylation ◽  
Normal Skin ◽  
Methylation Status ◽  
Cpg Islands ◽  
Treatment Strategies ◽  
Gene Promoter ◽  
Promoter Methylation Status ◽  
Pomc Gene ◽  
Methylation Patterns

Abstract Burn injuries frequently result in hypertrophic scars (HTSs), specifically when excision and grafting are delayed due to limited resources or patient complications. In patient populations with dark baseline pigmentation, one symptom of HTS that often occurs is dyspigmentation. The mechanism behind dyspigmentation has not been explored, and, as such, prevention and treatment strategies for this morbidity are lacking. The mechanism by which cells make pigment is controlled at the apex of the pathway by pro-opiomelanocortin (POMC), which is cleaved to its products alpha-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropin hormone (ACTH). α-MSH and ACTH secreted by keratinocytes bind to melanocortin 1 receptor (MC1R), expressed on melanocytes, to initiate melanogenesis. POMC protein expression is upregulated in hyperpigmented scar compared to hypopigmented scar by an unknown mechanism in a Duroc pig model of HTS. POMC RNA levels, as well as the POMC gene promoter methylation status were investigated as a possible mechanism. DNA was isolated from biopsies obtained from distinct areas of hyper- or hypopigmented scar and normal skin. DNA was bisulfite-converted, and amplified using two sets of primers to observe methylation patterns in two different CpG islands near the POMC promoter. Amplicons were then sequenced and methylation patterns were evaluated. POMC gene expression was significantly downregulated in hypopigmented scar compared to normal skin, consistent with previously reported protein expression levels. There were significant changes in methylation of the POMC promoter; however, none that would account for the development of hyper- or hypopigmentation. Future work will focus on other areas of POMC transcriptional regulation.

scholarly journals Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zijian Chen ◽  
Zenghong Huang ◽  
Yanxin Luo ◽  
Qi Zou ◽  
Liangliang Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Promoter Methylation ◽  
Expression Profiles ◽  
Methylation Status ◽  
Gene Promoter ◽  
Normal Mucosa ◽  
Suppressor Gene ◽  
Survival Outcome ◽  
Prognostic Models

Abstract Background Neurotrophic tropomyosin receptor kinases (NTRKs) are a gene family function as oncogene or tumor suppressor gene in distinct cancers. We aimed to investigate the methylation and expression profiles and prognostic value of NTRKs gene in colorectal cancer (CRC). Methods An analysis of DNA methylation and expression profiles in CRC patients was performed to explore the critical methylations within NTRKs genes. The methylation marker was validated in a retrospectively collected cohort of 229 CRC patients and tested in other tumor types from TCGA. DNA methylation status was determined by quantitative methylation-specific PCR (QMSP). Results The profiles in six CRC cohorts showed that NTRKs gene promoter was more frequently methylated in CRC compared to normal mucosa, which was associated with suppressed gene expression. We identified a specific methylated region within NTRK3 promoter targeted by cg27034819 and cg11525479 that best predicted survival outcome in CRC. NTRK3 promoter methylation showed independently predictive value for survival outcome in the validation cohort (P = 0.004, HR 2.688, 95% CI [1.355, 5.333]). Based on this, a nomogram predicting survival outcome was developed with a C-index of 0.705. Furthermore, the addition of NTRK3 promoter methylation improved the performance of currently-used prognostic model (AIC: 516.49 vs 513.91; LR: 39.06 vs 43.64, P = 0.032). Finally, NTRK3 promoter methylation also predicted survival in other tumors, including pancreatic cancer, glioblastoma and stomach adenocarcinoma. Conclusions This study highlights the essential value of NTRK3 methylation in prognostic evaluation and the potential to improve current prognostic models in CRC and other tumors.

scholarly journals Therapeutic Targets in Chronic Lymphocytic Leukemia

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3259
Author(s):  
Luca Laurenti ◽  
Dimitar G. Efremov
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Therapeutic Targets ◽  
Common Type ◽  
Lymphocytic Leukemia ◽  
Western Countries ◽  
B Cell Malignancy ◽  
Adult Leukemia ◽  
Cell Malignancy

Chronic lymphocytic leukemia (CLL) is a common B cell malignancy and is the most common type of adult leukemia in western countries [...]

Aberrant Genes Promoter Methylation in Neural Crest-Derived Tumors

2012 ◽  
Vol 27 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Annamaria La Torre ◽  
Lucia Anna Muscarella ◽  
Paola Parrella ◽  
Teresa Balsamo ◽  
Michele Bisceglia ◽  
...  
Keyword(s):  
Small Bowel ◽  
Neural Crest ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Cpg Islands ◽  
Aberrant Methylation ◽  
Tumor Type ◽  
Epigenetic Landscape ◽  
Molecular Biomarker

Disturbances in the epigenetic landscape by aberrant methylation of CpG islands can lead to inactivation of cancer-related genes in solid tumors. We analyzed the promoter methylation status of 6 genes previously reported as cancer-specific methylated (MCAM, SSBP2, NISCH, B4GALT1, KIF1A and RASSF1A) in 38 neural crest-derived tumors by quantitative methylation-specific real-time PCR (QMSP). The results demonstrated that the determination of the methylation status of RASSF1A is able to distinguish between normal and tumor samples in cutaneous melanomas, lung carcinoids and small bowel carcinoids. MCAM methylation levels were significantly higher in lung carcinoids tumors (p=0.001), suggesting that this alteration may represent a molecular biomarker in this tumor type.

scholarly journals Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 797-804
Author(s):  
V Pistoia ◽  
S Roncella ◽  
PF Di Celle ◽  
M Sessarego ◽  
G Cutrona ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Chromosomal Abnormalities ◽  
Cell Clone ◽  
Lymphoblastic Lymphoma ◽  
Lymphocytic Leukemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Chain Gene

A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed.

scholarly journals Analysis of smad4 gene promoter methylation in pancreatic and endometrial cancers

2017 ◽  
Vol 23 (2) ◽  
pp. 17-19
Author(s):  
Aleksandra Nikolic ◽  
Filip Opincal ◽  
Momcilo Ristanovic ◽  
Jovanka Trifunovic ◽  
Srbislav Knezevic ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Methylation Status ◽  
Gene Promoter ◽  
Promoter Hypermethylation ◽  
Surgical Removal ◽  
Smad4 Gene ◽  
Frequent Event ◽  
Cancer Types ◽  
Endometrial Cancers ◽  
Tumor Types

Background. Promoter hypermethylation of the SMAD4 gene has been registered in some cancer types, but in general doesn?t appear to be a frequent event in carcinogenesis. However, only a few published studies deal with this topic and not many cancer types have been analyzed. The aim of this study was to establish SMAD4 gene promoter methylation status in pancreatic and endometrial cancers. Methods. Patients included in the study (62 subjects) were diagnosed and surgically treated at the University of Belgrade, Clinical Center of Serbia. Patients with pancreatic carcinoma (17 subjects) underwent surgical removal of the pancreatic adenocarcinoma at the First Surgical Clinic, while the patients with endometrial carcinoma (45 subjects) underwent hysterectomy with adnexectomy at the Institute for Gynecology and Obstetrics. Extraction of DNA from fresh tissue samples was performed and the methylation status of the SMAD4 gene promoter was studied by a previously designed PCR-based HpaII and MspI restriction enzyme assay. The resulting PCR products were analyzed by electrophoresis in 2% agarose gels. Results. Neither of the analyzed samples was found to be hypermethylated. Conclusion. This is the first report on SMAD4 methylation status in pancreatic and endometrial tumor specimens, and supports the viewpoint that SMAD4 hypermethylation is not a common event in malignant tumors. Nevertheless, promoter hypermethylation remains a candidate mechanism for SMAD4 inactivation in malignant tissue as a potential cause of decreased or lost SMAD4 expression in certain tumor types, and should be further investigated in different tumor types and larger cohorts of patients.

scholarly journals Analysis of SEPT9 Gene Promoter Methylation Status in Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Aida Mirza Aghasi ◽  
Saied Ghorbian
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Gene Promoter ◽  
Sodium Metabisulfite ◽  
Significant Difference ◽  
Cancer Tissues

Introduction: The changes in the level of SEPT9 gene promoter methylation can contribute to the formation of esophageal squamous cell carcinoma. The aim of this study was to evaluate the level of changes in the level of SEPT9 gene promoter methylation in the esophageal squamous cell carcinoma. Methods: In the present case-control study, we collected 75 paraffin blocks of esophageal cancer tissues and 75 paraffin blocks healthy tissues, which were referred to the Noor-E-Nejat and Tabriz International Hospitals during 2013-2017. After DNA extraction and treatment with sodium metabisulfite, the changes of SEPT9 gene promoter methylation assessed using high resolution melting (HRM) technique. The data were analyzed by SPSS 22 and Chi-square test. Results: Our findings did not show a statistically significant difference between the changes of SEPT9 gene promoter methylation in cancer tissues compared to the healthy tissues (P=0.106). Conclusion: This study shows that SEPT9 gene promoter methylation cannot contribute to the esophageal squamous cell carcinoma cancerogenesis.  

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