Dergiler / Bezmiâlem Science / 2019 / Cilt: 7 - Sayı: 2

Aberrant Methylation Profile and Microsatellit Instability in Turkish Sporadic Colorectal Carcinoma

Sporadik Türk Kolorektal Karsinomalı Hastalarda Metilasyon Profili ve Mikrosatellit İnstabilitesi

Sayfa
86–94
DOI
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P73 was releated with left colorectal cancer and additionally it was related with the MSI.

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Amaç & Hipotez:Objective: Genomic DNA obtained from paraffin blocks of the intended colorectal cancer cases was evaluated for promoting colorectal cancer by investigating the promoter methylation of 6 different gene promoter regions and microsatellite instability.
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Temel Bulgular & Veri:Methods: DNA was isolated from the paraffin tissue of 76 sporadic colorectal cancer patients by cross sections from the areas determined to be tumorous.
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Sonuç & Katkı:P73 was releated with left colorectal cancer and additionally it was related with the MSI.
🔬Tür:Araştırma Makalesi
📍Kapsam:15 samples
⚙️Değişkenler:Alan Parametreleri

Özet

Objective: Genomic DNA obtained from paraffin blocks of the intended colorectal cancer cases was evaluated for promoting colorectal cancer by investigating the promoter methylation of 6 different gene promoter regions and microsatellite instability. Methods: DNA was isolated from the paraffin tissue of 76 sporadic colorectal cancer patients by cross sections from the areas determined to be tumorous. The methylation specific PCR (MS-PCR) method was used for these DNA samples fo rmethlylation studies in promoter region of six different APC, hMLH1, p16INK4A, p15, p73 and DAPK1 genes. In the same samples, the presence of microsatellite instability (MSI). Results: The fequencey of methylation was 24% for hMLH1, 31.5% for APC, 19.6% for DAPK1, 42.8% for p16, 30% for p15, 17% for p73. We calculated a methylation index (MI=ratio between the number of genes methylated and the number of genes analyzed). MI was ranged from 0-0.83, with an average of 0.271 corresponding to 1.6 genes /sample and median was 0.225 and there were 15 samples which doesn’t methylated in any loci. We analysed MSI in C-kit (21%), hMSH2 (18%) and APC (15%), microsatellite region. Conclusion: We observed APC methylation was common then the other population for Turkish patient. P16 was the most commenest methylated loci among the 6 of gene and it seems storongly related with female patients. P73 was releated with left colorectal cancer and additionally it was related with the MSI.

Abstract

Amaç: Bu çalışmanın amacı; kolorektal kanserli olguların parafin bloklarından elde edilen genomik DNA’da 6 farklı gen bölgesinin promoter metilasyonu ve mikrosatellite instabilitesini araştırmak ve bunların kolorektal kanser gelişimindeki önemini değerlendirmektir. Yöntemler: Yetmiş altı sporadik kolorektal kanserli olguya ait parafin dokusundan tümörlü olduğu belirlenen bölgelerden kesit alınarak DNA izolasyonu gerçekleştirilmiştir. Bu DNA örneklerinden metilasyon spesifik-PCZ (MS-PZR) yöntemi ile APC, hMLH1, p16INK4A, p15, p73 ve DAPK1 genlerine ait promoter bölgesi metilasyonu araştırılmıştır, aynı zamanda mikrosatellit instabilitesi (MSI) varlığı 3 farklı STR bölgesi incelenerek belirlenmiştir. Bulgular: Hasta örneklerimize ait genlerin metilasyon oranlarını hMLH1 için %24, APC için %31,5, DAPK1 için %19,6, p16 için %42,8, p15 için %30, p73 için %17 bulduk. Verilerin daha iyi anlaşılması için metilasyon indeksi (Mİ) hesaplandı. Bir örnek için metile olan gen sayısının analiz edilen gen sayısına oranı şeklinde hesapladığımız Mİ değeri 0-0,83 arasında bulundu. Ortalama Mİ 0,271 idi (1,6 gen/numuneye karşılık gelir) ve medyan değeri 0,225 idi. Herhangi bir lokusta metilasyona uğramayan 15 örnek vardı. MSİ’yi C-kit (21%), hMSH2 (18%) ve APC (15%) mikrosatellit bölgelerinde analiz ettik. Sonuç: Literatüre göre Türk populasyonunda APC metilasyonunun diğer popülasyondan daha sık olduğunu belirledik. P16 promoter metilasyonunun 6 gen arasında en fazla metilasyona uğrayan lokus olduğu ve kadın hastalarda daha sık metillendiği görülmüştür. P73 metilasyonu ise sıklıkla sol kolorektal kanserlerde belirlenmiş ve ek olarak da MSİ ile ilişkili bulunmuştur.

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Bu Makaleye Atıf Yap

EKMEKCI, C. G., GÜLLÜOĞLU, M., KAPRAN, Y., DİZDAROĞLU, F., ÖZBEK, U. (2019). Aberrant Methylation Profile and Microsatellit Instability in Turkish Sporadic Colorectal Carcinoma. Bezmiâlem Science, Cilt: 7 - Sayı: 2, 86–94. https://ajindex.com/articles/144291

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