Somatic mutation profiling of follicular thyroid cancer by next generation sequencing.
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.
Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland; Genomic Medicine, Medical University of Warsaw, Poland.
Michal
M
Swierniak
Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland; Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, Gliwice, Poland.
Aleksandra
A
Pfeifer
Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland; Department of Clinical Science, University of Bergen, Norway.
Tomasz
T
Stokowy
Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Dagmara
D
Rusinek
Tumor Pathology Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Mykola
M
Chekan
Tumor Pathology Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Dariusz
D
Lange
Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Jolanta
J
Krajewska
Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Małgorzata
M
Oczko-Wojciechowska
Department of Oncologic Surgery, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Agnieszka
A
Czarniecka
Department of Radiotherapy and Chemotherapy, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Michal
M
Jarzab
Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Barbara
B
Jarzab
Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland; Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, Warsaw, Poland. Electronic address: bwojtas@io.gliwice.pl.
Bartosz
B
Wojtas
D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D014157:Transcription Factors; D011494:Protein Kinases
Follicular thyroid cancer; Next generation sequencing; Somatic mutation