title: Detection of Circulating BRAF(V600E) in Patients with Papillary Thyroid Carcinoma.
abstract: BRAF(V600E) is a common mutation in papillary thyroid carcinoma (PTC) correlated with aggressive features. Our objective was to assess the feasibility and accuracy of a novel RNA-based blood assay to identify individuals with a high-risk tumor mutation in patients with PTC. Patients with benign or malignant thyroid disorders were included between September 2013 and July 2014 before either thyroidectomy (n = 62) or treatment of recurrent or metastatic PTC (n = 8). RNA was isolated from peripheral blood lymphocytes and reverse transcribed and followed by two rounds of nested PCR amplification with a restriction digest specific for wild-type BRAF. BRAF(V600E) levels were quantified with standardization curves. Circulating BRAF(V600E) levels were compared with BRAF mutation status from surgical pathologic DNA-based tissue assays. Testing characteristics and receiving-operator curve using tissue results as the gold standard were assessed. Matched blood and tissue assays for BRAF(V600E) were performed on 70 patients with PTC (stages I to IV, n = 48) or other (n = 22) thyroid tumors. Sixty-three percent of PTC patients tested positive for BRAF(V600E) with conventional tissue assays on surgical specimens. The correlation between the RNA-based blood assay and tissue BRAF status was 0.71. PTC patients harbor detectable BRAF(V600E) circulating tumor cells. This blood assay is feasible and has potential as a biomarker for prognosis, surveillance, clinical decision making, and assessment of treatment response to BRAF-targeted therapies.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: clubitz@partners.org.
authors.forename: Carrie C
authors.initials: CC
authors.lastname: Lubitz
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Sareh
authors.initials: S
authors.lastname: Parangi
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Holm
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: M Jordana
authors.initials: MJ
authors.lastname: Bernasconi
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Aislyn P
authors.initials: AP
authors.lastname: Schalck
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Hyunsuk
authors.initials: H
authors.lastname: Suh
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Economopoulos
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Gunda
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Donovan
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Wirth
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: David J
authors.initials: DJ
authors.lastname: Panka
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D002277:Carcinoma / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000097:blood* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf