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PAN-cancer identification of ncRNAs with biomarker potential in plasma

PAN-cancer identification of ncRNAs with biomarker potential in plasma

Non-coding RNAs (ncRNAs) are associated with various hallmarks of cancer including proliferation, invasion, migration and angiogenesis. Compared to protein-coding genes, their expression is often highly cell type specific, suggesting they may function as lineage survival oncogenes. As such, they can be exploited as attractive targets for nucleic acid based therapy with minimal risk for toxic side effects upon targeted inhibition. Furthermore, they are highly attractive as (non-invasive) biomarkers for diagnosis and treatment response monitoring of cancer patients. To identify cancer-type specific ncRNAs, we reprocessed small RNA and polyA+ RNA-sequencing data of The Cancer Genome Atlas (TCGA) and TARGET database, resulting in the annotation and quantification of miRNAs, isomiRs, sn(o)RNA fragments, tRNA fragments, mRNAs and lncRNAs in almost 12,000 patient samples covering 40 cancer types. Expression values were used to calculate an expression specificity score, resulting in more than 6000 ncRNA genes with a cancer-type specific expression pattern. Whereas cancer-type specific lncRNAs were identified in almost all cancer types, cancer-type specific miRNAs were found in only a subset of cancer types. Of note, isomiRs showed a higher level of cancer-type specificity compared to canonical miRs. To prioritize candidates, we integrated RNA-sequencing data from healthy controls. To enable sensitive detection these lncRNAs in circulation, we optimized RNA capture-sequencing for biofluids using custom probe sets. Currently, we are performing RNA capture-sequencing on a cohort of metastatic cancer patients representing 34 different cancer types. For each patient, total plasma RNA and RNA derived from plasma extra-cellular vesicles is available for analysis. These samples will also be analysed using small RNA-sequencing to evaluate cancer-type specific small ncRNAs.

Date: 6/16/17, 10am to 11am
Time: 6/16/17, 10am to 11am
Location: 4SCR1.1110
Format: Seminar/Conference
Speaker: Celine Everaert
Speaker Bio: Using bioinformatics to explore bigdata and to develop new cancer therapeutics and diagnostics.
Contact: Roseann Martinez - 32718 - rmartinez@mdanderson.org