Identification of a rare 3 bp BRAF gene deletion in a thyroid nodule by mutant enrichment with 3'-modified oligonucleotides polymerase chain reaction

Ann Lab Med. 2012 May;32(3):238-41. doi: 10.3343/alm.2012.32.3.238. Epub 2012 Apr 18.

Abstract

Papillary thyroid carcinoma (PTC) is the most common malignant thyroid tumor, and 36-69% of PTC cases are caused by mutations in the BRAF gene. The substitution of a valine for a glutamic acid (V600E) comprises up to 95-100% of BRAF mutations; therefore, most diagnostic methods, including allele-specific PCR and real-time PCR, are designed to detect this mutation. Nevertheless, other mutations can also comprise the genetic background of PTC. Recently, a novel and sensitive technique called mutant enrichment with 3'-modified oligonucleotides (MEMO) PCR has been introduced. When we applied allelespecific PCR and MEMO-PCR for the detection of the BRAF V600E mutation, we found an unusual 3' bp deletion mutation (c.1799_1801delTGA) only when using MEMO-PCR. This deletion results in the introduction of a glutamic acid into the B-Raf activation segment (p.V600_K601delinsE), leading to an elevated basal kinase activity of BRAF. This is the first report of a rare 3 bp BRAF deletion in a PTC patient that could not be detected by allele-specific PCR.

Keywords: BRAF; Deletion; Korean; Mutant enrichment with 3'-modified oligonucleotides (MEMO) PCR; Mutation; Papillary thyroid carcinoma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Carcinoma
  • Carcinoma, Papillary
  • Female
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Oligonucleotides / genetics
  • Polymerase Chain Reaction / methods*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Sequence Deletion
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology
  • Thyroid Nodule / metabolism

Substances

  • Oligonucleotides
  • Proto-Oncogene Proteins B-raf