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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: 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. Methods: 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. Results: 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\u2013deletion variants (INDELs), and 99 copy-number variations (CNVs) were identified in the TCTs. Moreover, an OTU deubiquitinase, ubiquitin aldehyde\u2013binding protein 2 (OTUB2), with a deletion mutation enhanced the proliferation of thyroid cancer cells in both in vitro and in vivo experiments. Conclusion: 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.<\/jats:p>","DOI":"10.31083\/fbl49970","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:36:33Z","timestamp":1774949793000},"source":"Crossref","is-referenced-by-count":0,"title":["OTUB2 Mutation Promotes Thyroid Collision Tumor\u2019s Insights From the Whole-exome Sequence"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8941-7560","authenticated-orcid":true,"given":"Ying","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Thyroid and Breast Surgery, Shandong Provincial Third Hospital, Shandong University, 250031 Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery, Shandong Provincial Third Hospital, Shandong University, 250031 Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5054-0842","authenticated-orcid":true,"given":"Mengyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery, Shandong Provincial Third Hospital, Shandong University, 250031 Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Bojoga A, St\u0103nescu L, Badiu C. 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Epitranscriptic regulation of HRAS by N6-methyladenosine drives tumor progression. Proceedings of the National Academy of Sciences of the United States of America. 2023; 120: e2302291120.","DOI":"10.1073\/pnas.2302291120"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Ma Y, Sun Y. miR-29a-3p inhibits growth, proliferation, and invasion of papillary thyroid carcinoma by suppressing NF-\u03baB signaling via direct targeting of OTUB2. Cancer Management and Research. 2019; 11: 13\u201323.","DOI":"10.2147\/CMAR.S184781"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Li Y, Chen X, Xu X, Chen C, Min M, Liang D, et al. OTUB2 contributes to vascular calcification in chronic kidney disease via the YAP-mediated transcription of PFKFB3. Theranostics. 2025; 15: 1185\u20131204.","DOI":"10.7150\/thno.98660"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Mei F, Deng D, Cao Z, Lou L, Chen K, Hu M, et al. Deubiquitination of RIPK3 by OTUB2 potentiates neuronal necroptosis after ischemic stroke. EMBO Molecular Medicine. 2025; 17: 679\u2013695.","DOI":"10.1038\/s44321-025-00206-6"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Mao JT, Xue B, Lu QY, Lundmark L, Burns W, Yang J, et al. Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT. Life Sciences. 2023; 318: 121492.","DOI":"10.1016\/j.lfs.2023.121492"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Zhang C, Chen B, Jiao A, Li F, Sun N, Zhang G, et al. miR-663a inhibits tumor growth and invasion by regulating TGF-\u03b21 in hepatocellular carcinoma. BMC Cancer. 2018; 18: 1179.","DOI":"10.1186\/s12885-018-5016-z"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Wang G, Chen L, Jian W, Fang L. 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