1. Diffüz Büyük B-Hücreli Lenfomada GADD45? Metilasyonunun Olası Rolü: Lenfoma Progresyonunu ve Doku Tutulumunu Etkiler mi?
- Author
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Mehmet Hilmi Dogu, Emre Tepeli, Vildan Caner, Sibel Hacioglu, Gulseren Bagci, Nilay Şen Türk, Ismail Sari, Ikbal Cansu Baris, Ali Keskin, Ozge Can, and Ozan Cetin
- Subjects
Male ,Pathology ,very elderly ,Nucleic Acid Denaturation ,preschool child ,Lymphoid hyperplasia ,Pseudolymphoma ,immune system diseases ,hemic and lymphatic diseases ,middle aged ,DNA denaturation ,genetics ,Genetik ve Kalıtım ,Hücre Biyolojisi ,Hematoloji ,Onkoloji ,Patoloji ,high resolution melting analysis ,Child ,Promoter Regions, Genetic ,comparative study ,Regulation of gene expression ,Aged, 80 and over ,clinical article ,large cell lymphoma ,larynx squamous cell carcinoma ,DNA methylation ,adult ,disease course ,Intracellular Signaling Peptides and Proteins ,Hematology ,Methylation ,lcsh:Diseases of the blood and blood-forming organs ,Diffuse large B-cell lymphoma ,gene expression regulation ,DNA, Neoplasm ,Cell cycle ,GADD45? ,unclassified drug ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,aged ,female ,Organ Specificity ,Child, Preschool ,immunohistochemistry ,Disease Progression ,young adult ,GADD45γ ,Lymphoma, Large B-Cell, Diffuse ,medicine.symptom ,cancer tissue ,Research Article ,medicine.medical_specialty ,lcsh:Internal medicine ,Adolescent ,Biology ,Article ,cancer growth ,GADD45G protein, human ,growth arrest and DNA damage inducible protein 45 gamma ,promoter region ,tumor protein ,medicine ,Humans ,signal peptide ,controlled study ,Epigenetics ,human ,lcsh:RC31-1245 ,lymphoid tissue ,protein methylation ,protein expression ,lcsh:RC633-647.5 ,growth arrest and DNA damage inducible protein 45 ,cancer staging ,disease association ,antibody specificity ,Infant ,lymphoid hyperplasia ,DNA ,medicine.disease ,DNA isolation ,human tissue ,diffuse large B cell lymphoma ,Lymphoma ,physiology ,pathology ,biosynthesis ,metabolism - Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia.Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry.GADD45γ methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040).The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ.Amaç: Diffüz büyük B-hücreli lenfoma (DBBHL) yetişkin bireylerde Hodgkin-dışı lenfomaların en yaygın tipidir ve klinik, immünofenotipik ve genetik özellikler açısından heterojen özellikler taşıması ile karakterizedir. DBBHL patogenezinde hücre döngüsü ve apoptoz regülasyonunu bozan farklı mekanizmalar rol oynamaktadır. Growth arrest DNA damage-inducible 45 (GADD45γ), bu mekanizmalarda yer alan önemli bir gen ailesidir. Bu çalışmanın amaçları DBBHL doku örnekleri ve reaktif lenfoid hiperplazili bireylerin reaktif lenfoid doku örneklerinde GADD45γ metilasyon sıklığını belirlemek, GADD45γ metilasyonu ile protein ekspresyonu arasındaki ilişkiyi değerlendirmek ve DBBHL olgularında metilasyon durumunun klinikopatolojik parametrelerle ilişkisini araştırmaktır. Gereç ve Yöntemler: Bu çalışmada 36 adet DBBHL doku örnekleri ve 40 adet malign-olmayan reaktif lenfoid doku örnekleri analiz edildi. GADD45γ metilasyon durumunu belirlemek için metilasyona-duyarlı yüksek çözünürlüklü erime eğrisi analizi kullanıldı. GADD45γ protein ekspresyonu immünohistokimyasal analiz ile belirlendi. Bulgular: DBBHL’de GADD45γ metilasyonunun sık olduğu belirlendi (%50). Aynı zamanda, erken evre ile karşılaştırıldığında ileri evre tümörlerde GADD45γ metilasyonu istatistiksel olarak anlamlı düzeyde yüksekti (p=0,041). Ancak, GADD45γ metilasyon yokluğunun primer anatomik yerleşim olarak nodal tutulumla ilişkili olduğu belirlendi (p=0,040). Sonuç: Bu çalışmanın sonuçları solid tümörlerin aksine, DBBHL’de GADD45γ metilasyon sıklığının yüksek olduğunu ve GADD45γ geninde gözlenen bu epigenetik değişimin, hastalığın progresyonu ile ilişkili olabileceğini göstermektedir. Buna ek olarak, nodal tutulum daha çok GADD45γ metile olmayan olgularda gözlenmektedir.
- Published
- 2015