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Published on: September 15, 2023
Novel rearrangements involving the RET gene in papillary thyroid carcinoma
Julia Isabelle Staubitz1, Arno Schad2, Erik Springer2
1Section of Endocrine Surgery, Department of General, Visceral and Transplantation Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany.
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.
Insights
Novel gene fusions RUFY2-RET and KIAA1468-RET were identified in papillary thyroid carcinoma (PTC). These RET rearrangements, previously seen in lung cancer, offer new insights into thyroid cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gene fusions drive tumorigenesis in papillary thyroid carcinoma (PTC).
- RET proto-oncogene rearrangements are frequent in PTC, with over 15 known partner genes.
- Next-generation sequencing expands the understanding of RET rearrangements in PTC (RET-PTC).
Observation:
- Targeted next-generation sequencing and Sanger sequencing were used for two BRAF-wild type PTC cases.
- UniProt database was queried for protein alterations from RET rearrangements.
- RUFY2-RET and KIAA1468-RET fusion genes were detected and absent in normal patient tissue.
Findings:
- The RUFY2-RET rearrangement fuses the RET tyrosine kinase domain with RUN and coiled-coil domains.
- The KIAA1468-RET rearrangement results in a fusion with LisH and coiled-coil domains.
- These novel RET/PTC rearrangements involve the fusion of the RET tyrosine kinase to regulatory domains of RUFY2 and KIAA1468.
Implications:
- RUFY2-RET and KIAA1468-RET are novel RET/PTC rearrangements.
- Identical fusions have been previously reported in non-small cell lung cancer.
- These findings highlight conserved oncogenic pathways across different cancer types.
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