title: Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.
abstract: OBJECTIVE
  Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group.
  
  
  METHODS
  Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString's nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected.
  
  
  RESULTS
  Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations.
  
  
  CONCLUSIONS
  In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Seoul, Korea.
authors.forename: Bo Mi
authors.initials: BM
authors.lastname: Ku
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hae Su
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.affiliation: Samsung Biomedical Research Institute, Seoul, Korea.
authors.forename: Young Lyun
authors.initials: YL
authors.lastname: Oh
authors.affiliation: Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
authors.forename: Mineui
authors.initials: M
authors.lastname: Hong
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Han-Sin
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young-Ik
authors.initials: YI
authors.lastname: Son
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chung-Hwan
authors.initials: CH
authors.lastname: Baek
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D011905:Genes, ras; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012008:Recurrence; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; PIK3CA; Papillary thyroid carcinoma; RET