KRAS mutation analysis in genomic DNA isolated from formalin-fixed paraffin-embedded ovarian tissue: evaluation of a strip-based reverse-hybridisation assay

J Clin Pathol. 2011 Mar;64(3):252-6. doi: 10.1136/jcp.2010.081414. Epub 2011 Jan 22.

Abstract

Aims: To evaluate a reverse-hybridisation assay (strip assay) designed for the sensitive detection of 10 mutations in codons 12 and 13 of the KRAS gene. The strip assay relies on mutant-enriched PCR followed by reverse-hybridisation of biotinylated amplification products to oligonucleotide probes immobilised as an array of parallel lines on nitrocellulose test strips.

Methods: The strip assay was used to analyse genomic DNA isolated from 120 formalin-fixed paraffin-embedded (FFPE) ovarian tissue samples. The samples were analysed in parallel using a biochip-based protocol (biochip assay) covering the same mutation spectrum, and results were compared with respect to sensitivity, specificity and operational input.

Results: The strip assay identified 19 (16%) of 120 FFPE samples to carry a KRAS mutation; results were in agreement with those obtained by biochip hybridisation. Both assays had an analytical sensitivity of 1% when performed on FFPE-extracted DNA with approximately the same operational input needed for post-PCR processing. In contrast to the biochip assay, strip assay hybridisation may be automated to a large extent.

Conclusions: The strip assay is an accurate and sensitive tool for the low to medium throughput detection of KRAS mutation in genomic DNA isolated from FFPE tissue.

Publication types

  • Evaluation Study

MeSH terms

  • DNA, Neoplasm / genetics
  • Female
  • Formaldehyde
  • Humans
  • Mutation*
  • Ovarian Neoplasms / genetics*
  • Paraffin Embedding
  • Polymerase Chain Reaction / methods
  • Protein Array Analysis / methods
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Reagent Strips
  • Sensitivity and Specificity
  • Tissue Fixation / methods
  • ras Proteins / genetics*

Substances

  • DNA, Neoplasm
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Reagent Strips
  • Formaldehyde
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins