Upregulation of INS-IGF2 read-through expression and identification of a novel INS-IGF2 splice variant in insulinomas

Oncol Rep. 2016 Nov;36(5):2653-2662. doi: 10.3892/or.2016.5132. Epub 2016 Sep 23.


Fusion transcripts arising from the combination of exons residing on neighboring genes on the same chromosome may give rise to chimeric or novel proteins. Such read-through transcripts have been detected in different cancers where they may be of pathogenetic interest. In this study, we describe for the first time the expression of a read-through transcript in insulinomas, a functioning neuroendocrine pancreatic neoplasm. The read-through transcript INS-IGF2, composed of exons from the two genes proinsulin precursor (INS) and insulin‑like growth factor 2 (IGF2), both mapping to chromosomal subband 11p15.5, was highly expressed in the two insulinomas analyzed. More precisely, version 2 of the INS-IGF2 transcript was expressed, indicating possible expression of the chimeric INS-IGF2 protein. We further identified a novel splice variant of the INS-IGF2 read-through transcript in one of the insulinomas, composed of exon 1 of INS3 and exons of IGF2. In the same tumor, we found high expression of INS3 and the presence of the A allele at SNP rs689. SNP rs689 has been previously described to regulate splicing of the INS transcript, indicating that this regulatory mechanism also affects splicing of INS-IGF2. The identification of the INS-IGF2 read-through transcript specifically in tumor tissue but not in normal pancreatic tissue suggests that high expression of INS-IGF2 could be neoplasia‑specific. These results may have potential clinical applications given that the read-through transcript could be used as a biomarker in insulinoma patients.

MeSH terms

  • Adult
  • Alleles
  • Chromosomes, Human, Pair 11 / genetics
  • Exons / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin / genetics*
  • Insulin-Like Growth Factor II / biosynthesis
  • Insulin-Like Growth Factor II / genetics*
  • Insulinoma / genetics*
  • Insulinoma / pathology
  • Male
  • Pancreas / pathology
  • Polymorphism, Single Nucleotide
  • Protein Isoforms / genetics*
  • RNA Splicing / genetics
  • Transcriptional Activation / genetics


  • IGF2 protein, human
  • Insulin
  • Protein Isoforms
  • Insulin-Like Growth Factor II