title: High prevalence and mutual exclusivity of genetic alterations in the phosphatidylinositol-3-kinase/akt pathway in thyroid tumors.
abstract: BACKGROUND
  Genetic alterations in the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and their role in thyroid tumor pathogenesis in Chinese people remain undefined.
  
  
  OBJECTIVE
  The objective of the study was to examine the major genetic alterations and their relationship in the PI3K/Akt pathway in differentiated thyroid tumors in a Chinese cohort.
  
  
  METHODS
  We used real-time quantitative PCR for the analysis of PIK3CA copy gain and direct DNA sequencing for the detection of PIK3CA, RAS, and PTEN mutations on genomic DNA isolated from 234 thyroid tumors, including 31 follicular thyroid cancer (FTC), 141 papillary thyroid cancer (PTC), and 62 follicular thyroid adenoma (FTA).
  
  
  RESULTS
  We found PIK3CA copy gain (defined as four or more copies) in nine of 31 FTC (29%), 20 of 141 PTC (14%), and five of 62 FTA (8%); PIK3CA gene mutations in four of 31 FTC (13%), one of 141 PTC (1%), and none of 62 FTA (0%); Ras mutations in three of 31 FTC (10%) and none of the 141 PTC and 62 FTA; and PTEN mutations in two of 31 FTC (6%) and none of 62 FTA (0%). Collectively, nine of 31 FTC (29%) vs. none of 62 FTA (0%) (P < 0.01) harbored one of the mutations, and when PIK3CA copy gain was included, 16 of 31 FTC (52%) vs. five of 62 FTA (8%) (P < 0.01) harbored any genetic alteration in the PI3K/Akt pathway. Mutual exclusivity was seen among all these PI3K/Akt pathway-related genetic alterations in all thyroid tumors except for two cases that harbored two genetic alterations.
  
  
  CONCLUSIONS
  These data from a Chinese cohort provide further genetic evidence suggesting that dysregulated PI3K/Akt pathway plays a significant role in the pathogenesis of thyroid tumors, particularly FTC.
authors.affiliation: Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Yangang
authors.initials: Y
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Meiju
authors.initials: M
authors.lastname: Ji
authors.forename: Shihua
authors.initials: S
authors.lastname: Zhao
authors.forename: Shengli
authors.initials: S
authors.lastname: Yan
authors.forename: Xianlu
authors.initials: X
authors.lastname: Sun
authors.forename: Dingxie
authors.initials: D
authors.lastname: Liu
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
authors.forename: Guangwu
authors.initials: G
authors.lastname: Zhu
authors.forename: Stephen
authors.initials: S
authors.lastname: Condouris
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002291:Carcinoma, Papillary / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism*; D015995:Prevalence; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018631:ras Proteins; C484760:PIK3CA protein, human; C494929:PTEN protein, human