Myelodisplastik sendrom tanılı hastalarda tet2, asxl1, ıdh1/2 gen polimorfizmi ve klinikle ilişkisinin değerlendirilmesi
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Dosyalar
Tarih
2016
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Miyelodisplastik sendrom (MDS) periferik sitopeni, karakteristik morfolojik bulgular ve kemik iliğinde sitogenetik anormallikler dahil çeşitli bozuklukların olduğu heterojen bir hastalıktır. IDH1 (İzositrat dehidrogenaz; 2q33.3 lokalize), IDH2 (15q26.1), TET2 (TET ten eleven ten-onkogen aile üyesi 2; 4q24) ve ASXL1 (Additional Sex Combs-Like 1; 20q11.21). gibi bazı genlerin MDS patogenezinde rolü bildirilmiştir. MDS’de seçilen genlerin polimorfizminin ve allel sıklığının belirlenmesini amaçladık. 100 MDS hastası IDH1 rs11554137, IDH2 rs121913503, rs267606870, TET2 rs763480 ve ASXL1 rs2208131 genotipi için değerlendirildi. Periferik kandan genomik Deoksiribonükleik asit (DNA) elde edildi. Polimeraz zincir reaksiyonu (PCR) TaqMan Single-nucleotide polymorphism (SNP) genotip belirlemek için (Applied Biosystems, Foster City, CA) ABI 7500 Fast kullanılmış her mutasyonu allelik dağılımında sequence detection Systems software, SDS 2,0) dizileme sistemleri kullanılmıştır. MDS’de medyan tanı yaşı 76 olup bizim çalışmamızda medyan yaş 65 (24-89) saptandı. Tanı yaşı, cinsiyet, WHO sınıfı, Uluslararası Prognostik Skorlama Sistemi (IPSS) grubu, tanıda bakılan hemogram parametreleri [Lökosit (WBC), Hemoglobin (Hb), Trombosit (PLT)] açısından polimorfizmler (yabanıl tip, heterozigot, homozigot mutant) karşılaştırıldığında istatiksel anlamlı farklılık bulunmadı. Sadece ASXL1 heterozigot+homozigot olan grubun medyan tanı yaşı anlamlı olarak daha yüksek bulundu (p=0,048). Herhangi bir polimorfizmin prognostik etkisi saptanmadı. TET2 heterozigot polimorfik grup azasitidin (AZA) tedavi yanıtı yabanıl tipe göre istatiksel anlamlı yüksek bulundu (p=0,042) Sonuç olarak bizim çalışmamız bu genlerin polimorfizminin değerlendirilmesi için başlangıç noktası olup yeni çalışmalara rehberlik edebilir.
Myelodysplastic syndromes (MDS) represent heterogeneous group of disorders with a variety of features including peripheral cytopenia, characteristic morphological findings and cytogenetic abnormalities in bone marrow. Some genes are reported to be involved in the pathogenesis of MDS such as IDH1 (Isocitrate dehydrogenase; localised to 2q33.3), IDH2 (15q26.1), TET2 (TET oncogene family member 2; 4q24) and ASXL1 (Additional Sex Combs-Like 1;20q11.21). Thus, identifying the recent mutations of these genes and genotyping the patients for these selected mutations might have clinical impact in MDS. We aimed to determine the genotype distribution and allele frequency of selected genes in MDS cases. Total 100 patients were genotyped for 5 mutations as IDH1 rs11554137, IDH2 rs121913503–rs267606870, TET2 rs763480, and ASXL1 rs2208131. DNA was isolated from each patients' peripheral blood samples. Following PCR reactions with TaqMan SNP genotyping assay (Applied Biosystems, Foster City, CA) via ABI 7500 Fast instrument, the cases were genotyped with "sequence detection Systems software, SDS 2,0) for allelic discrimination for each mutation. The median age at diagnosis of MDS is 76 in our study revealed a median age of 65 (24-89). Age at diagnosis, gender, WHO classification, IPSS group, diagnosis (WBC-Hb-PLT) compared with polymorphisms (wild-type, heterozygous, homozygous mutants) were not statistically significant differences. Only ASXL1 heterozygous group median age at diagnosis was significantly higher than homozygous (p=0,048). No significant association with the prognostic impact any of the polymorphisms. TET2 heterozygous polymorphic group of azacitidine (AZA) treatment response was significantly higher compared to the wild type. (p=0,042). Our study is the starting point for genotyping these polymorphism that might have clinical guidance for MDSs.
Myelodysplastic syndromes (MDS) represent heterogeneous group of disorders with a variety of features including peripheral cytopenia, characteristic morphological findings and cytogenetic abnormalities in bone marrow. Some genes are reported to be involved in the pathogenesis of MDS such as IDH1 (Isocitrate dehydrogenase; localised to 2q33.3), IDH2 (15q26.1), TET2 (TET oncogene family member 2; 4q24) and ASXL1 (Additional Sex Combs-Like 1;20q11.21). Thus, identifying the recent mutations of these genes and genotyping the patients for these selected mutations might have clinical impact in MDS. We aimed to determine the genotype distribution and allele frequency of selected genes in MDS cases. Total 100 patients were genotyped for 5 mutations as IDH1 rs11554137, IDH2 rs121913503–rs267606870, TET2 rs763480, and ASXL1 rs2208131. DNA was isolated from each patients' peripheral blood samples. Following PCR reactions with TaqMan SNP genotyping assay (Applied Biosystems, Foster City, CA) via ABI 7500 Fast instrument, the cases were genotyped with "sequence detection Systems software, SDS 2,0) for allelic discrimination for each mutation. The median age at diagnosis of MDS is 76 in our study revealed a median age of 65 (24-89). Age at diagnosis, gender, WHO classification, IPSS group, diagnosis (WBC-Hb-PLT) compared with polymorphisms (wild-type, heterozygous, homozygous mutants) were not statistically significant differences. Only ASXL1 heterozygous group median age at diagnosis was significantly higher than homozygous (p=0,048). No significant association with the prognostic impact any of the polymorphisms. TET2 heterozygous polymorphic group of azacitidine (AZA) treatment response was significantly higher compared to the wild type. (p=0,042). Our study is the starting point for genotyping these polymorphism that might have clinical guidance for MDSs.
Açıklama
Anahtar Kelimeler
MDS, SNP, TET2, ASXL1, IDH1-2
