Novel rearrangements involving the RET gene in papillary thyroid carcinoma

Cancer Genet. 2019 Jan:230:13-20. doi: 10.1016/j.cancergen.2018.11.002. Epub 2018 Nov 13.


Background: In the field of gene fusions driving tumorigenesis in papillary thyroid carcinoma (PTC), rearrangement of the proto-oncogene RET is the most frequent alteration. Apart from the most common rearrangement of RET to CCDC6, more than 15 partner genes are yet reported. The landscape of RET rearrangements in PTC ("RET-PTC") can notably be enlarged by modern targeted next-generation sequencing, indicating similarities between oncogenic pathways in other cancer types with identical genetic alterations.

Methods: Targeted next-generation sequencing was performed for two cases of BRAF-wild type PTC with confirmation of the results by Sanger sequencing. A "UniProt" database research was performed to assess protein alterations resulting from RET rearrangements.

Results: RUFY2-RET and KIAA1468-RET were detected. The fusion genes were not present in normal tissue of the index patients. The rearrangement RUFY2-RET lead to a fusion of the RET tyrosine kinase domain to a RUN domain and a coiled-coil domain. For KIAA1468-RET, a fusion to a LisH domain and two coiled-coil domains resulted.

Conclusions: RUFY2-RET and KIAA1468-RET are novel RET/PTC rearrangements. The fusions were previously described in non-small cell lung cancer. The rearrangement results in a fusion of the RET tyrosine kinase to regulatory domains of RUFY2 and KIAA1468.

Keywords: KIAA1468; Papillary thyroid carcinoma; RET gene; RET/PTC; RUFY2.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / genetics
  • Female
  • Gene Rearrangement
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Nuclear Proteins
  • Oncogene Proteins, Fusion / genetics*
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret / genetics*
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Neoplasms / genetics*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • MAS1 protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Mas
  • RELCH protein, human
  • RUFY2 protein, human
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • ret-PTC fusion oncoproteins, human