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Cancer Epigenomic Insights Reported by International Consortia Members

NEW YORK (GenomeWeb) – The epigenetic and regulatory underpinnings for a handful of cancer types are coming into sharper focus as investigators from several international teams report on work done through the International Human Epigenome Consortium (IHEC).

Along with two dozen new studies published in Cell Press journals this week, the IHEC collection includes papers that came out over the course of the year in several other journals. The set touches on everything from development and immune response epigenetics to autism epigenetics and tools used for doing large-scale epigenetic research. It also contains insights into epigenetic features found in breast cancer, various leukemia types, and a form of childhood tumor that is best known for developing in the brain and kidney.

Using an in silico approach called epigenomic deconvolution, for example, researchers from Baylor College of Medicine and elsewhere assessed cell type composition, methylation, and expression patterns in breast tumors profiled for the Cancer Genome Atlas project. Their study, appearing in Cell Reports, revealed ties between tumor subtype and immune cell infiltration, along with metabolic features related to tumor and stromal cell composition.

"By providing information about the epigenomic and transcriptomic states of both cancerous epithelial and non-epithelial tumor cells, the method enables the study of heterotypic interactions driving tumor progression," the authors wrote. "The most striking pattern that emerged from our analyses is metabolic coupling between epithelium and stroma that seems to be related to the degree of adiposity of the stroma." 

A Spanish-led team involved in the BLUEPRINT Epigenome Project published a Cell Reports paper that provided clues to leukemia epigenetics — from mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma in the lymphoid lineage to myeloid lineage-derived leukemias such as acute promyelocytic leukemia and acute myeloid leukemia — by profiling DNA methylation patterns associated with immune cell lineage specification.

"We show clear trends in methylation patterns that are distinct in the innate and adaptive arms of the human immune system, both globally and in relation to consistently positioned nucleosomes," authors of that study wrote. "Cancer samples from the two lineages are further polarized, suggesting the involvement of distinct lineage-specific epigenetic mechanisms."

Another Cell Reports study out this week specifically looked at the regulatory effects of the oncogenic AML1-ETO gene fusion in acute myeloid leukemia. For that analysis, investigators from Italy and the Netherlands used a combination of gene knockdown assays, ChIP-seq, RNA-seq, and other methods to characterize AML1-ETO binding sites and related expression changes in cells from individuals with AML, identifying transcription factors that seem to prevent over-expression of the oncogene fusion.

Still other studies appearing in Cancer Cell and Immunity dealt with DNA methylation and epigenetic imprinting features of mantle cell lymphoma and transcriptional features of tumor-infiltrating T regulatory cells in lung or colorectal cancers, respectively.

Finally, for a Cancer Cell study originally published in March, researchers in Canada and the US presented new molecular sub-groups of malignant rhabdoid tumors, a type of childhood tumor that most often appears in the kidney or brain. used a combination of genome sequencing, bisulfite sequencing, RNA sequencing, microRNA sequencing, and/or chromatin immunoprecipitation sequencing to profile the heterogeneous molecular features found in dozens of primary malignant rhabdoid tumor samples, detecting clusters of expression- and methylation-based tumor sub-groups in the process.

The Scan

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Just Make It

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Nucleic Acids Research Papers on OncoDB, mBodyMap, Genomicus

In Nucleic Acids Research this week: database to analyze large cancer datasets, human body microbe database, and more.