Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B-cell precursor acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer. Although the genetic determinants underlying disease onset remain unclear, epigenetic modifications including DNA methylation are suggested to contribute significantly to leukemogenesis. Using the Illumina 450K array, we assessed DNA methylation in matched tumor-normal samples of 46 childhood patients with pre-B ALL, extending single CpG-site resolution analysis of the pre-B ALL methylome beyond CpG-islands (CGI). Unsupervised hierarchical clustering of CpG-site neighborhood, gene, or microRNA (miRNA) gene-associated methylation levels separated the tumor cohort according to major pre-B ALL subtypes, and methylation in CGIs, CGI shores, and in regions around the transcription start site was found to significantly correlate with transcript expression. Focusing on samples carrying the t(12;21) ETV6-RUNX1 fusion, we identified 119 subtype-specific high-confidence marker CpG-loci. Pathway analyses linked the CpG-loci-associated genes with hematopoiesis and cancer. Further integration with whole-transcriptome data showed the effects of methylation on expression of 17 potential drivers of leukemogenesis. Independent validation of array methylation and sequencing-derived transcript expression with Sequenom Epityper technology and real-time quantitative reverse transcriptase PCR, respectively, indicates more than 80% empirical accuracy of our genome-wide findings. In summary, genome-wide DNA methylation profiling enabled us to separate pre-B ALL according to major subtypes, to map epigenetic biomarkers specific for the t(12;21) subtype, and through a combined methylome and transcriptome approach to identify downstream effects on candidate drivers of leukemogenesis.
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PMID:Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia. 2372 52

Gene fusions are observed in abnormal chromosomal rearrangements such as translocations in hematopoietic malignancies, especially leukemia subtypes. Hence, it is critical to obtain correct information about these rearrangements in order to apply proper treatment techniques. To identify abnormal molecular changes in patients with leukemia, we developed a multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) protocol and investigated more than 140 gene fusions resulting from variations of 29 prevalent chromosomal rearrangements along with EVI1 and TLX1 oncogenic expression in the presence of optimized primers. The potential of the MRT-PCR method was approved by evaluating the available cell lines as positive control and confirmed by sequencing. Samples from 53 patients afflicted with hematopoiesis malignancies were analyzed. Results revealed at least one chromosomal rearrangement in 69% of acute myeloid leukemia subjects, 64% of acute lymphoblastic leukemia subjects, and 81% of chronic myeloid leukemia subjects, as well as a subject with hypereosinophilic syndrome. Also, five novel fusion variants were detected. Results of this study also showed that chromosomal rearrangements, both alone and in conjunction with other rearrangements, are involved in leukemogenesis. Moreover, it was found that EVI1 is a suitable hallmark for hematopoietic malignancies.
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PMID:Molecular analysis of more than 140 gene fusion variants and aberrant activation of EVI1 and TLX1 in hematological malignancies. 2877 53


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