Xia Li | bioRxiv Science

bioRxiv2016

The Cancer Epitope Trees of 23 Early Cervical Cancers in Chinese Women

Emerging evidences suggest the heterogeneity of cancers limits the efficacy of immunotherapy. To search for optimal therapeutic targets, we used whole-exome sequencing data from 23 early cervical tumors from Chinese women to investigate the hierarchical structure of the somatic mutations and the predicted neo-epitopes based on their strong binding with major histocompatibility complex class I molecules. We found each tumor carried 117 mutations and 61 neo-epitopes in average and displayed a unique phylogenic tree and \"cancer neo-epitope tree\" comprising different compositions of mutations or neo-epitopes. Conceivably, the neo-epitopes at the top of the tree shared by all cancer cells are the optimal therapeutic targets that might lead to a cure. Human papillomavirus can be used as therapeutic target in only a proportion of cases where the integrated genome exits without active infection. Therefore, the \"cancer neo-epitope tree\" will serve as an important source to determine of the optimal immunotherapeutic target.

Cancer Biology↗

bioRxiv2014

Genome-wide DNA methylome analysis reveals novel epigenetically dysregulated non-coding RNAs in human breast cancer

The development of human breast cancer is driven by changes in the genetic and epigenetic landscape of the cell. Despite growing appreciation of the importance of epigenetics in breast cancers, our knowledge of epigenetic alterations of non-coding RNAs (ncRNAs) in breast cancers remains limited. Here, we explored the epigenetic patterns of ncRNAs in breast cancers via a sequencing-based comparative methylome analysis, mainly focusing on two most popular ncRNA biotypes, long non-coding RNAs (lncRNAs) and miRNAs. Besides global hypomethylation and extensive CpG islands (CGIs) hypermethylation, we observed widely aberrant methylation in the promoters of ncRNAs, which was higher than that of protein-coding genes. Specifically, intergenic ncRNAs were observed to contribute a large slice of the aberrantly methylated ncRNA promoters. Moreover, we summarized five patterns of ncRNA promoter aberrant methylation in the context of genomic CGIs, where aberrant methylation occurred not only on the CGIs, but also flanking regions and CGI sparse promoters. Integration with transcriptional datasets, we found that the ncRNA promoter methylation events were associated with transcriptional changes. Furthermore, a panel of ncRNAs were identified as biomarkers that were able to discriminate between disease phenotypes (AUCs>0.90). Finally, the potential functions for aberrantly methylated ncRNAs were predicted based on similar patterns, adjacency and/or target genes, highlighting that ncRNAs and coding genes coordinately mediated pathways dysregulation in the development and progression of breast cancers. This study presents the aberrant methylation patterns of ncRNAs, which will be a highly valuable resource for investigations at understanding epigenetic regulation of breast cancers.\n\n[Supplemental material is available online at www.genome.org.]

Bioinformatics↗