OTUB2 Mutation Promotes Thyroid Collision Tumor's Insights From the Whole-exome Sequence

Thyroid collision tumors (TCTs) are rare thyroid malignancies characterized by the coexistence of distinct tumor types. We investigated the histopathology, immunohistochemistry, and gene mutations to comprehensively characterize the heterogeneity of TCTs.

Immunohistochemistry (IHC), hematoxylin and eosin (HE) staining, and Congo red staining were performed to characterize tumor markers. DNA concentrations of all samples were measured using the Qubit DNA Assay Kit in the Qubit 2.0 fluorometer. Somatic mutations were analyzed using the Genomic Identification of Significant Targets in Cancer (GISTIC) and the NCBI-ClinVar, dbSNP, COSMIC, and HGMD databases. Bioinformatic enrichments were constructed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases, the OncodriveCLUST software, Cytoscape, and Circos.

Immunohistochemistry staining of papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) samples showed several distinct biomarkers. According to whole-exome sequencing, a total of 76 single-nucleotide variants (SNVs), 12 insertion-deletion variants (INDELs), and 99 copy-number variations (CNVs) were identified in the TCTs. Moreover, an OTU deubiquitinase, ubiquitin aldehyde-binding protein 2 (OTUB2), with a deletion mutation enhanced the proliferation of thyroid cancer cells in both in vitro and in vivo experiments.

HRas proto-oncogene (HRAS) and STAG2 cohesin complex component (STAG2) were synchronously identified as the driver genes, while the OTUB2 deletion mutation may contribute to tumor proliferation and disease progression in TCTs.