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Cancer Genet. 2019 Jul 5;238:10-17. doi: 10.1016/j.cancergen.2019.07.002. [Epub ahead of print]

ANKRD26-RET - A novel gene fusion involving RET in papillary thyroid carcinoma.

Author information

1
Section of Endocrine Surgery, Department of General, Visceral and Transplantation Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany. Electronic address: julia.staubitz@unimedizin-mainz.de.
2
Section of Endocrine Surgery, Department of General, Visceral and Transplantation Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany.
3
Institute of Pathology, University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany.
4
Department of General, Visceral and Transplantation Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany.
5
Cell Biology Unit, University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstraße 1, D-55131 Mainz, Germany.

Abstract

BACKGROUND:

Rearrangements of RET are drivers of oncogenesis, traceable in different cancer types as papillary thyroid carcinoma (PTC), non-small cell lung cancer, colorectal or breast cancer. Anchored multiplex PCR based next-generation sequencing (NGS) can detect RET rearrangements involving previously unknown partner genes.

METHODS:

A sample of PTC underwent NGS, following detection of RET rearrangement by fluorescence in situ hybridization. Expression analysis of ANKRD26 and RET was performed for the tumor harboring ANKRD26-RET, for corresponding normal thyroid tissue and PTC tumors with representative genetic alterations (BRAFV600E, CCDC6-RET), complemented by a comparative search in the "UniProt" database.

RESULTS:

NGS analysis resulted in the discovery of the fusion ANKRD26-RET. ANKRD26 mRNA was expressed in all PTC tumors (ANKRD26-RET, BRAFV600E, CCDC6-RET) and in normal thyroid tissue, whereas RET mRNA was detected only in the tumors with RET rearrangement. On protein level, ANKRD26-RET combines the RET tyrosine kinase to ankyrin repeat and coiled-coil domains.

CONCLUSIONS:

ANKRD26-RET is a novel rearrangement of the RET gene, associated with RET expression in thyroid tissue. The result is a fusion of the RET tyrosine kinase to prominent protein-protein interaction motifs. Further studies are required to investigate the influence of different RET rearrangements on metastasis and disease-free survival in PTC.

KEYWORDS:

ANKRD26; Expression analysis RET; Papillary thyroid carcinoma; RET; RET rearrangement; RET/PTC

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