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

Cancer Genet. 2019 Oct;238:10-17. doi: 10.1016/j.cancergen.2019.07.002. Epub 2019 Jul 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Fusion*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Proto-Oncogene Proteins c-ret / genetics*
  • Survival Analysis
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Neoplasms / genetics*

Substances

  • ANKRD26 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-ret
  • RET protein, human