title: Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors.
abstract: BACKGROUND
  As in many other human cancers, overactivation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway occurs frequently in thyroid cancer, but the mechanism is not completely clear.
  
  
  OBJECTIVE
  Because activating mutations and genomic amplification of the PIK3CA gene, which encodes the p110a catalytic subunit of PI3K, are common in many cancers, we sought to investigate this phenomenon in thyroid tumors.
  
  
  METHODS
  To search for PIK3CA mutations, we isolated genomic DNA from primary thyroid tumors of various types and performed direct sequencing of the exons of PIK3CA gene that carry the most common mutations in other cancers. We used real-time quantitative PCR to investigate genomic amplification of the PIK3CA gene.
  
  
  RESULTS
  We found no PIK3CA gene mutations in 37 benign thyroid adenomas, 52 papillary thyroid cancers, 25 follicular thyroid cancers, 13 anaplastic thyroid cancers, 13 medullary thyroid cancers, and seven thyroid tumor cell lines. We found a C3075T single-nucleotide polymorphism in exon 20 of this gene in two cases. With a copy number of 4 or more defined as amplification, we found PIK3CA gene amplification in four of 34 (12%) benign thyroid adenomas, three of 59 (5%) papillary thyroid cancer, five of 21 (24%) follicular thyroid cancer, none of 14 (0%) medullary thyroid cancer, and five of seven (71%) thyroid tumor cell lines. The PIK3CA gene amplification and consequent Akt activation were confirmed by fluorescence in situ hybridization and Western blotting studies using cell lines, respectively.
  
  
  CONCLUSIONS
  These data suggest that mutation of the PIK3CA gene is not common, but its amplification is relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mambo
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Guo
authors.forename: Shuiying
authors.initials: S
authors.lastname: Hu
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Gollin
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
authors.forename: Paul W
authors.initials: PW
authors.lastname: Ladenson
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
mesh_terms: D058534:Class I Phosphatidylinositol 3-Kinases; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C484760:PIK3CA protein, human; C494918:AKT1 protein, human