Halil HANCI, Birol TOPÇU, Seval AKPINAR, BurhanTURGUT, Bahadır BATAR

WWOX GEN İFADESİNİN KRONİK LENFOSİTİK LÖSEMİ İLE İLİŞKİSİ

Amaç: WW alanı içeren oksidoredüktaz (WWOX) geni kromozom 16q23.3-q24.1 bölgesinde bulunmaktadır ve yaygın kromozomal frajilbölge, FRA16D, içermektedir. WWOX geni 46 kDa moleküler ağırlığında WWOX tümör baskılayıcı proteini kodlar. Birçok insankanserlerinde WWOX lokusunda heterozigozite kaybı (LOH), WWOX promoter hipermetilasyonu ve sonuç olarak Wwox ifadesi kaybıveya azalması bildirilmiştir. Ayrıca, son çalışmalar çeşitli kanser tiplerinde Wwox eksikliğinin kötü prognoz ile ilişkili olduğunugöstermiştir. Kronik lenfositik löseminin (KLL) klinik özellikleri ve genetik anomalileri iyi tanımlanmıştır, fakat moleküler detaylar halenaraştırılmaktadır. WWOX ifadesi seviyeleri KLL için olası bir biyobelirteç olabilir. Bildiğimiz kadarıyla literatürde KLL’de WWOX’ın tanı veprognostik önemi ile ilgili kanıtlar bulunmamaktadır. Çalışmamızda, KLL hastalarında ve sağlıklı kontrollerde WWOX ifadesi düzeylerinitanımlamayı ve KLL hastalarında WWOX ifadesini klinik özelliklerine göre analiz etmeyi amaçladık.Materyal ve Metot: Bu çalışmayı 40 KLL hastasında ve 26 sağlıklı kontrolde gerçekleştirdik. WWOX ifadesi seviyelerini ters transkriptazkantitatif PCR (RT-QPCR) tekniğini kullanarak analiz ettik.Bulgular: Sonuçlarımız WWOX ifadesinin KLL hastalarında sağlıklı kontrol grubuna göre anlamlı derecede yüksek olduğunu gösterdi(P

Association of WWOX Gene Expression with Chronic Lymphocytic Leukemia

Aim: The WW domain-containing oxidoreductase (WWOX) gene is located on chromosome 16q23.3-q24.1 and contains the common chromosomal fragile site, FRA16D. The WWOX gene encodes a Wwox tumor suppressor protein with a molecular weight of 46 kDa. Loss of heterozygosity (LOH) at the WWOX locus, promoter hypermethylation of the WWOX promoter, and consequently Wwox expression loss or reduction has been reported in a large fraction of many human cancers. Also, recent studies have shown that Wwox deficiency is associated with poor prognosis in various types of cancer. Clinical features and genetic anomalies of chronic lymphocytic leukemia (CLL) are well defined, but molecular details are still under investigation. WWOX expression levels could be a possible biomarker for CLL. As much as we know, there is no evidence for diagnostic and prognostic significance of Wwox in CLL. In our study, we aimed to define the expression levels of WWOX in CLL patients and also to analyze the WWOX expression in CLL patients with regard to their clinical characteristics. Materials and Methods: We performed this study in 40 CLL patients and 26 healthy controls. We analyzed the WWOX expression levels by using reverse transcriptase-quantitative PCR (RT-QPCR). Results: Our results showed that WWOX expression was significantly higher in CLL patients compared to healthy control group (P0.05). Results: Our results showed that WWOX expression was significantly higher in CLL patients compared to healthy control group (P0.05). Conclusion: Abnormal transcription variants of WWOX gene can be associated with abnormal protein isoforms and these isoforms can change the tumor suppressive effects of WWOX gene in CLL patients.

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