Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
İkbal Cansu
İC
Barış
Pamukkale University Faculty of Medicine, Department of Medical Biology, Denizli, Turkey Phone: +90 258 296 24 94 E-mail: vildancaner@yahoo.com, vcaner@pau.edu.tr.
Vildan
V
Caner
Nilay
N
Şen Türk
İsmail
İ
Sarı
Sibel
S
Hacıoğlu
Mehmet Hilmi
MH
Doğu
Ozan
O
Çetin
Emre
E
Tepeli
Özge
Ö
Can
Gülseren
G
Bağcı
Ali
A
Keskin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009691:Nucleic Acid Denaturation; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D019310:Pseudolymphoma / Q000378:metabolism; D055815:Young Adult; D000097642:GADD45 Proteins
D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C485654:GADD45G protein, human; D000097642:GADD45 Proteins