title: Trisomy 8 Acute Myeloid Leukemia Analysis Reveals New Insights of DNA Methylome with Identification of HHEX as Potential Diagnostic Marker.
abstract: Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI (P = 7.88 × 10(-11)) identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML.
authors: Centre for Haemato-Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom. ; Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors: Marwa H
authors: MH
authors: Saied
authors: Centre for Haemato-Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom. ; Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors: Jacek
authors: J
authors: Marzec
authors: Centre for Haemato-Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors: Sabah
authors: S
authors: Khalid
authors: Centre for Haemato-Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors: Paul
authors: P
authors: Smith
authors: Centre for Haemato-Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors: Gael
authors: G
authors: Molloy
authors: Centre for Haemato-Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors: Bryan D
authors: BD
authors: Young
keywords: CGI shores; HHEX; MeDIP-seq; trisomy 8