title: Identification of a rare 3 bp BRAF gene deletion in a thyroid nodule by mutant enrichment with 3'-modified oligonucleotides polymerase chain reaction.
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.
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Jang
authors.forename: Seung-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Young Lyun
authors.initials: YL
authors.lastname: Oh
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Kim
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002277:Carcinoma; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009841:Oligonucleotides / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology; D016606:Thyroid Nodule / Q000378:metabolism
chemical_list: D009841:Oligonucleotides; D048493:Proto-Oncogene Proteins B-raf