OP27 – Comprehensive Molecular Analysis of Thyroid Cancer: Diagnosis, Predictors of Disease Progression and Targets for Directed Therapy

      Rasamny, JK1; Moscatello, Augustine1; Dermigny, Katharine2; Jourdy,Deya1; Lando, Tali1; Kamat, Ameet1; Budenz, Cameron1; Berzofsky, Craig1; Jones, Melanie2;  Gupta, Anvita2; O’Connell, Timmy2; Suslina, Nina3; Iacob, Codrin4; Shin, Edward3; Schantz, Stimson3;  Schwarcz, Monica5; Tiwari, Raj1,2; Geliebter, Jan1,2 1 Department of Otolaryngology, New York Medical College, Valhalla, NY, USA 2 Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA 3 Department of Otolaryngology, New York Eye and Ear Infirmary, Mt. Sinai SOM, NY, USA 4 Department of Pathology, New York Eye and Ear Infirmary, Mt. Sinai SOM, NY, USA 5 Department of Medicine, New York Medical College, Valhalla, NY, USA   Background/Purpose: Papillary thyroid cancer (PTC) will account for ~80% of the ~56,870 new thyroid cancer cases in 2017 (ACS).  ~20% of FNABs are indeterminate and require resection, despite ~50% being benign, driving unnecessary surgeries, underscoring the need for diagnostic/prognostic biomarkers. Objectives: To determine molecular signatures of PTC and matched, normal thyroid tissue (MNTT) to identify diagnostic/ prognostic markers, and molecular targets for personalized therapy. Methods: Following consenting of NYEEI patients, surgery, and diagnosis by the pathologist, RNA was prepared from samples, rRNA eliminated, and RNA-Seq performed (Illumina HiSeq 2000).    rRNA elimination, instead of poly-A selection, enriches for noncoding RNAs.   STARv2.5.2b/ htseq-countv0.6.1 and DESeq2 were used to align raw sequences, and measure transcript abundance. Results: RNASeq of PTC and MNTT from 56 patients yielded ~50 million reads/sample, with >93% of reads aligned to the human reference genome.  12,122 transcripts achieved the 1.5 fold level differential expression (PTC vs. MNTT) with p< 0.05, including 6071 protein–coding transcripts, 1703 lncRNAs, 1399 antisense transcripts, 295 snRNAs/snoRNAs, and 318 sense-intronic and overlapping transcripts.  Novel transcripts with altered expression were identified. Discussion: Our RNA processing technique has enriched our RNASeq database for novel, noncoding RNAs that are known to play critical roles in cell homeostasis.  The biological significance of differentially expressed RNA transcripts is being investigated using pathway analysis software. Conclusion: We have identified over 12,000 coding and noncoding RNAs that are differentially expressed in PTC vs. MNTT.  The detailed analysis of our database should yield novel, diagnostic/prognostic biomarkers, and therapeutic targets.


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