Targeted next generation sequencing identifies somatic mutations and gene fusions in papillary thyroid carcinoma

Abstract

138 papillary thyroid carcinoma (PTC) samples were assessed for somatic mutation profile and fusion genes by targeted resequencing using a cancer panel (ThyGenCapTM) targeting 244 cancer-related genes and 20 potential fusion genes. At least one genetic alteration (including mutations and fusion genes) was observed in 118/138 (85.5%) samples. The most frequently mutated gene was BRAF V600E (57.2%). Moreover, we identified 11 fusion genes including eight previously reported ones and three novel fusion genes, UEVLD-RET, OSBPL9-BRAF, and SQSTM1-NTRK3. Alterations affecting the mitogen-activated protein kinase (MAPK) signaling pathway components were seen in 69.6% of the PTC cases and all of these driver mutations were mutually exclusive. Univariate analysis ascertained that the fusion genes were strongly associated with distinct clinicopathological characteristics, such as young age, local invasion, extensive metastasis, and disease stage. In conclusion, our approach facilitated simultaneous high-throughput detection of gene fusions and somatic mutations in PTC samples.

Genomic Characterization of Differentiated Thyroid Carcinoma

“…In 2016, our group also described the mutational profile of 77 Korean patients with cPTC based on an RNA-seq analysis [6]. In our study cohort, 71.43% of cPTC patients harbored BRAF V600E , which is a slightly higher rate than has been reported in other studies [417181920]. An NRAS mutation was only found in 1.3% of study subjects, whereas 18.18% of cases of cPTC had gene rearrangements in RET (5.18%), BRAF (3.9%), NTRK1/3 (3.9%), ALK (1.3%), FGFR2 (1.3%), and THADA (1.3%).…”

“…Another frequently altered gene, G protein-coupled receptor LPAR4 (2.7%), was also discovered, and the malignant transformation of PTC through LPAR4 mutation was revealed. In 2017, another Chinese PTC cohort with 138 patients was analyzed using the targeted sequencing method [ 19 ]. This study displayed a similar incidence of BRAF V600E (57.25%) as the TCGA cohort, whereas only 2.17% of tumors harbored a RAS mutation ( KRAS only).…”

NTRK and other recently described kinase fusion positive uterine sarcomas: A review of a group of rare neoplasms

“…As with other tyrosine kinases, the oncogenic fusion mechanism consists of juxtaposing of the 3′ region of RET gene with the 5′ region of a partner gene resulting in a constitutive and ligand independent receptor activation 69,70 . RET fusions have been reported in 4.4% 71 to 6.8% 72 of papillary thyroid carcinomas, especially in populations exposed to radiation, 73 in 1% to 3% of non‐small cell lung carcinomas and in 0.2% to 1.6% of colorectal carcinomas 74,75 …”

A case of Warthin-like papillary thyroid carcinoma with diffuse sclerosing stroma and a novel RET mutation: a new entity or a combined tumour?

“…Moreover, we found a 5% allele frequency of BRAF mutation; such a low value may be explained because of other non-neoplastic cells commixed with neoplastic ones (i.e., lymphocytes, stromal cells), highlighting the clinical relevance of using a high-sensitivity technique, such as next-generation sequencing (tumoural cell content of specimens tested: 20%). Recently, some authors identified a genetic alteration of the MAPK (Mitogen-Activating Protein Kinase) pathway in about 70% of PTC using NGS, detecting either point mutations or structural rearrangements [20]. This technique allowed the recognition of other novel molecular alteration in PTC, as in our case [21].…”