Constitutional and somatic methylation status of DMRH19 and KvDMR in Wilms tumor patients

Genetics and Molecular Biology

Leila C.a. Cardoso²  Jair A. Tenorio Castaño¹  Hanna S. Pereira¹  Maria Angélica De F.d. Lima¹  Anna Cláudia E. Dos Santos²  Paulo S. De Faria¹  Sima Ferman¹  Héctor N. Seuánez²  Julián B. Nevado¹  José Carlos Cabral De Almeida¹  Pablo Lapunzina¹  Fernando R. Vargas² 

[1],Universidade Federal do Rio de Janeiro Departamento de Genética Rio de Janeiro RJ ,Brazil

关键词: epigenetic;    histopathology;    methylation;    MS-MLPA;    pyrosequencing;   

DOI  :  10.1590/S1415-47572012005000073

来源: SciELO

【 摘 要 】

The most frequent epigenetic alterations in Wilms tumor (WT) occur at WT2, assigned to 11p15. WT2 consists of two domains: telomeric domain 1 (DMRH19) that contains the IGF2 gene and an imprinted maternally expressed transcript (H19) and centromeric domain 2 (KvDMR) that contains the genes KCNQ1, KCNQ1OT1 and CDKN1C. In this work, we used pyrosequencing and MS-MLPA to compare the methylation patterns of DMRH19/KvDMR in blood and tumor samples from 40 WT patients. Normal constitutional KvDMR methylation indicated that most of the epigenetic alterations in WT occur at DMRH19. Constitutional DMRH19 hypermethylation (HM DMRH19) was observed in two patients with Beckwith-Wiedemann syndrome. Pyrosequencing and MS-MLPA showed HM DMRH19 in 28/34 tumor samples: 16/34 with isolated HM DMRH19 and 12/34 with concomitant HM DMRH19 and KvDMR hypomethylation, indicating paternal uniparental disomy. With the exception of one blood sample, the MS-MLPA and pyrosequencing findings were concordant. Diffuse or focal anaplasia was present in five tumor samples and was associated with isolated somatic HM DMRH19 in four of them. Constitutional 11p15 methylation abnormalities were present in 5% of the samples and somatic abnormalities in the majority of tumors. Combined analysis of DMRH19/KvDMR by pyrosequencing and MS-MLPA is beneficial for characterizing epigenetic anomalies in WT, and MS-MLPA is useful and reliable for estimation of DNA methylation in a clinical setting.

【 授权许可】

CC BY   
 All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License