Endocrine Abstracts

JOINT2685

Background: Follicular differentiated thyroid cancer (FDTC) is the most common endocrine cancer, globally. Next-generation sequencing (NGS) in thyroid cancer allows for high-throughput genetic sequencing with quick turnover. NGS Studies on papillary thyroid cancer are scanty from South East Asia. This study harnesses the power of Whole Exome Next-Generation Sequencing (WES) to unravel pan-exomic mutations in thyroid cancer samples. The primary objectives include correlating genomic changes with clinicopathologic features and unraveling the intricate mechanisms steering disease onset and progression.

Methods: We selected 22 FDTC cases. All of them underwent total thyroidectomy with neck dissection as needed. Tumour tissue samples extracted and paraffin embedded, were taken from exvivo specimens. Sample processing, DNA extraction, cDNA preparation and PCR amplification was performed. Mutation analysis with a thyroid cellular pathway specific 56-gene mutation panel using real-time PCR and ThyroSeq v2 on the Ion Torrent PGM sequencer was employed. Common single nucleotide polymorphisms (SNPs) with a minor allele frequency of >0. 05 were excluded. Mutations were also manually checked using the Integrated Genomics Viewer v2. 4. 10 to filter out false positives.

Results: The analysis found mutations commonly in BRAF (16), CDKN2A (10), NRAS (7), PI3KCA (8), RET (4), RAS (13) and TP53 (3) genes. The common mutations found in the samples was RET (M918T), NRAS (Q61R), BRAF (V600E) and missense mutation in TP53 (c. 217 – c. 1178). A mutation has also been identified in KMT2D gene in two of the patient samples. BRAF, CDKN2A, PI3KCA were more common in papillary cancer. RAS, NRAS, RET mutations were common in follicular cancer. TP53 and KMT2D were seen only in poorly differentiated cancer.

Conclusion: NGS appears to be helpful in risk assessement, prognostication and study of tumour biology in clinical setting. More prospective studies are needed for its routine use at clinical level.

Key Words: Thyroid cancer; BRAF gene; RAS gene; Genomics; Mutation