KRAS insertions in colorectal cancer: what do we know about unusual KRAS mutations?

Exp Mol Pathol. 2014 Apr;96(2):257-60. doi: 10.1016/j.yexmp.2014.02.014. Epub 2014 Mar 2.

Abstract

Introduction: KRAS mutations are negative predictors of the response to anti-EGFR therapy in colorectal carcinomas (CRCs). Point mutations in codons 12, 13, and 61 are the most common KRAS mutations in CRC. There are few reports on insertions in KRAS, and little is known about its ability to activate the RAS pathway. The scarcity of data regarding insertion frequencies and nucleotide additions in KRAS impedes the management of patients with such mutations. We present data on KRAS insertions in CRC and discuss a case.

Materials and methods: Pyrosequencing and Sanger sequencing were performed to identify KRAS and BRAF mutations in paraffin-embedded samples of CRC. Expression of mismatch repair proteins was examined by immunohistochemistry.

Results: We detected a GGT insertion between codons 12 and 13 (c.36_37insGGT;p.G12_G13insG) in a CRC patient. We found that insertions in KRAS is very rare in CRC and that the most frequent type of insertion is c.36_37insGGT.

Conclusions: KRAS gene insertions represent a diagnostic and clinical challenge due to the difficult and unusual pyrosequencing findings and the lack of information regarding its clinical impact.

Keywords: Colorectal cancer; Genetics; KRAS mutation; Molecular pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Child, Preschool
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutagenesis, Insertional / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins