Recurrent oncogenic ZC3H18 mutations stabilize endogenous retroviral RNA.

Endogenous retroviral (ERV) RNA is highly expressed in cancer, although the molecular causes and consequences remain unknown. We found that ZC3H18 (Z18), a component of multiple nuclear RNA surveillance complexes, has recurrent truncating mutations in cancer. We show that Z18 mutations are oncogenic and that Z18 plays an evolutionarily conserved role in nuclear RNA surveillance of ERV RNA.

Chromosomal rearrangements and instability caused by the LINE-1 retrotransposon.

LINE-1 (L1) retrotransposition is widespread in many cancers, especially those with a high burden of chromosomal rearrangements. However, whether and to what degree L1 activity directly impacts genome integrity is unclear. Here, we apply whole-genome sequencing to experimental models of L1 expression to comprehensively define the spectrum of genomic changes caused by L1.

Non-small Cell Lung Cancer Epigenomes Exhibit Altered DNA Methylation in Smokers and Never-smokers.

Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment outcome. To determine the potential contribution of DNAmethylation alterations to tumor phenotype in non-small cell lung cancer (NSCLC) in both smoker and never-smoker patients, we performed genome-wide profiling of DNA methylation in 17 primary NSCLC tumors and 10 matched normal lung samples using the complementary assays, methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation sensitive restriction enzyme sequencing (MRE-seq). We reported recurrent methylation changes in the promoters of several genes, many previously implicated in cancer, including FAM83A and SEPT9 (hypomethylation), as well as PCDH7, NKX2-1, and SOX17 (hypermethylation).

Capture Methylation-Sensitive Restriction Enzyme Sequencing (Capture MRE-Seq) for Methylation Analysis of Highly Degraded DNA Samples.

Understanding the impact of DNA methylation within different disease contexts often requires accurate assessment of these modifications in a genome-wide fashion. Frequently, patient-derived tissues stored in long-term hospital tissue banks have been preserved using formalin-fixation paraffin-embedding (FFPE). While these samples can comprise valuable resources for studying disease, the fixation process ultimately compromises the DNA's integrity and leads to degradation.

Developmental Pathways Are Epigenetically Reprogrammed during Lung Cancer Brain Metastasis.

Unlabelled: Non-small cell lung cancer (NSCLC) is one of the most commonly diagnosed and deadliest cancers worldwide, with roughly half of all patients initially presenting with both primary and metastatic disease. While the major events in the metastatic cascade have been identified, a mechanistic understanding of how NSCLC routinely and successfully colonizes the brain is largely unknown. Recent studies have begun demonstrating the role of epigenetic misregulation during tumorigenesis and metastasis, including widespread changes in DNA methylation and histone modifications.

Common DNA methylation dynamics in endometriod adenocarcinoma and glioblastoma suggest universal epigenomic alterations in tumorigenesis.

Trends in altered DNA methylation have been defined across human cancers, revealing global loss of methylation (hypomethylation) and focal gain of methylation (hypermethylation) as frequent cancer hallmarks. Although many cancers share these trends, little is known about the specific differences in DNA methylation changes across cancer types, particularly outside of promoters. Here, we present a comprehensive comparison of DNA methylation changes between two distinct cancers, endometrioid adenocarcinoma (EAC) and glioblastoma multiforme (GBM), to elucidate common rules of methylation dysregulation and changes unique to cancers derived from specific cells.