Identification of a novel, recurrent SLC44A1-PRKCA fusion in papillary glioneuronal tumor

Brain Pathol. 2013 Mar;23(2):121-8. doi: 10.1111/j.1750-3639.2012.00612.x. Epub 2012 Jul 23.

Abstract

Mixed neuronal-glial tumors are rare and challenging to subclassify. One recently recognized variant, papillary glioneuronal tumor (PGNT), is characterized by prominent pseudopapillary structures and glioneuronal elements. We identified a novel translocation, t(9;17)(q31;q24), as the sole karyotypic anomaly in two PGNTs. A fluorescence in situ hybridization (FISH)-based positional cloning strategy revealed SLC44A1, a member of the choline transporter-like protein family, and PRKCA, a protein kinase C family member of serine/threonine-specific protein kinases, as the 9q31 and 17q24 breakpoint candidate genes, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) analysis using a forward primer from SLC44A1 exon 5 and a reverse primer from PRKCA exon 10 confirmed the presence of a SLC44A1-PRKCA fusion product in both tumors. Sequencing of each chimeric transcript uncovered an identical fusion cDNA junction occurring between SLC44A1 exon 15 and PRKCA exon 9. A dual-color breakpoint-spanning probe set custom-designed for interphase cell recognition of the translocation event identified the fusion in a third PGNT. These results suggest that the t(9;17)(q31;q24) with the resultant novel fusion oncogene SLC44A1-PRKCA is the defining molecular feature of PGNT that may be responsible for its pathogenesis. The FISH and RT-PCR assays developed in this study can serve as valuable diagnostic adjuncts for this rare disease entity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / genetics*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Carcinoma, Papillary / surgery
  • Child
  • Cytogenetics
  • Female
  • Frontal Lobe / pathology
  • Frontal Lobe / surgery
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Oncogene Fusion*
  • Organic Cation Transport Proteins / genetics*
  • Parietal Lobe / pathology
  • Parietal Lobe / surgery
  • Protein Kinase C-alpha / genetics*
  • Temporal Lobe / pathology
  • Temporal Lobe / surgery

Substances

  • Antigens, CD
  • Organic Cation Transport Proteins
  • SLC44A1 protein, human
  • PRKCA protein, human
  • Protein Kinase C-alpha