A novel RET/PTC variant detected in a pediatric patient with papillary thyroid cancer without ionization history

Hum Pathol. 2015 Dec;46(12):1962-9. doi: 10.1016/j.humpath.2015.08.013. Epub 2015 Sep 15.

Abstract

Papillary thyroid carcinoma (PTC) is the most frequent type of thyroid cancer. Its development is often caused by the formation of RET/PTC fused genes. RET/PTC1 is the most prevalent form, where exon 1 of CCDC6 gene is fused with the intracellular portion of RET protooncogene starting with exon 12. We have discovered a novel RET/PTC1 variant which we have named RET/PTC1ex9 in metastatic PTC of 8-year-old boy. RET/PTC1ex9 detection was performed by real-time polymerase chain reaction with melting curve analysis and subsequent Sanger and next-generation sequencing. A fusion of exon 1 of CCDC6 with exon 9 of extracellular domain of RET followed by exon 12 of RET was revealed. This is the first RET/PTC variant among PTC cases that contain the extracellular part of RET. This observation could be probably explained by incorrect splicing of RET due to the somatic 32-bp deletion in exon-intron 11 boundary of RET.

Keywords: Fused gene; Next-generation sequencing; Papillary thyroid cancer; RET gene; RET/PTC rearrangement; RET/PTC1ex9.

Publication types

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

MeSH terms

  • Carcinoma / genetics*
  • Carcinoma, Papillary
  • Child
  • Gene Rearrangement
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Patched Receptors
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-ret / genetics*
  • Receptors, Cell Surface / genetics*
  • Sequence Analysis, DNA
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics*

Substances

  • Oncogene Proteins, Fusion
  • Patched Receptors
  • Receptors, Cell Surface
  • Proto-Oncogene Proteins c-ret
  • RET protein, human