Mutation Profile of B-Raf Gene Analyzed by fully Automated System and Clinical Features in Japanese Melanoma Patients

Pathol Oncol Res. 2017 Jan;23(1):181-188. doi: 10.1007/s12253-016-0121-2. Epub 2016 Oct 21.

Abstract

BRAF gene mutations have been observed in 30-50 % of malignant melanoma patients. Recent development of therapeutic intervention using BRAF inhibitors requires an accurate and rapid detection system for BRAF mutations. In addition, the clinical characteristics of the melanoma associated with BRAF mutations in Japanese patients have not been investigated on a large scale evaluation. We recently established quenching probe system (QP) for detection of an activating BRAF mutation, V600E and evaluated 113 melanoma samples diagnosed in Saga University Hospital from 1982 to 2011. The QP system includes fully automated genotyping, based on analysis of the probe DNA melting curve, which binds the target mutated site using a fluorescent guanine quenched probe. BRAF mutations were detected in 54 of 115 (47 %) including 51 of V600E and 3 of V600 K in Japanese melanoma cases. Among clinical subtypes of melanoma, nodular melanoma showed high frequency (12 of 15; 80 %) of mutation followed by superficial spreading melanoma (13 of 26; 50 %). The QP system is a simple and sensitive method to determine BRAF V600E mutation, and will be useful tool for patient-oriented therapy with BRAF inhibitors.

Keywords: B-raf; Melanoma; Molecular targeted therapy; Tyrosine kinase inhibitors.

MeSH terms

  • Aged
  • Asian People / genetics*
  • Cell Line, Tumor
  • DNA Mutational Analysis / methods
  • Female
  • Genotype
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Middle Aged
  • Mutation / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf