Somatic mutation profiling of follicular thyroid cancer by next generation sequencing

• Published in: Molecular and cellular endocrinology 2016-09, Vol.433, p.130-137
• Main Authors: Swierniak, Michal, Pfeifer, Aleksandra, Stokowy, Tomasz, Rusinek, Dagmara, Chekan, Mykola, Lange, Dariusz, Krajewska, Jolanta, Oczko-Wojciechowska, Małgorzata, Czarniecka, Agnieszka, Jarzab, Michal, Jarzab, Barbara, Wojtas, Bartosz
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Follicular - genetics; Adult; Aged; Aged, 80 and over; Epigenesis, Genetic - genetics; Female; Follicular thyroid cancer; High-Throughput Nucleotide Sequencing - methods; Humans; Male; Middle Aged; Mutation - genetics; Next generation sequencing; Oncogenes - genetics; Protein Kinases - genetics; Somatic mutation; Transcription Factors - genetics
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2016.06.007

The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity. •The spectrum of somatic alterations in follicular thyroid tumors is largely unknown.•Cancer genes in 82 thyroid tissue samples were tested by next generation sequencing.•Single nucleotide variants were most common; large structural changes were rare.•New somatic alterations were found in genes as well as non-coding regions.•Distinct tumor somatic alterations suggested previously unreported heterogeneity.