title: PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous cell carcinoma.
abstract: BACKGROUND
  Recent genomic evidence suggests frequent phosphatidylinositide 3-kinase (PI3K) pathway activation in human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma. Mutations/amplification of the gene encoding p110α catalytic subunit of phosphoinositide 3-kinase (PIK3CA), loss of phosphatase and tensin homolog (PTEN) and HRAS mutations are known to activate PI3K pathway.
  
  
  RESULTS
  PIK3CA mutations were identified by Sanger sequencing in 23 of 75 (31%) HPV-positive oropharyngeal carcinomas, including exon 9 (p.E545K [n = 10] and p.E542K [n = 5]) or exon 20 (p.H1047Y, n = 2) mutations. Five rare and one novel (p.R537Q) PIK3CA mutations were identified. HRAS mutation (p.Q61L) was detected in 1 of 62 tested cases. PIK3CA amplification by fluorescence in situ hybridization (FISH) was identified in 4 cases (4/21, 20%), while PTEN loss was seen in 7 (7/21, 33%) cases (chromosome 10 monosomy [n = 4], homozygous deletion [n = 3]).
  
  
  CONCLUSIONS
  Overall, genetic alterations that likely lead to PI3K pathway activation were identified in 34 of 75 cases (45%) and did not correlate with disease specific survival. These findings offer a molecular rationale for therapeutic targeting of PI3K pathway in patients with HPV-positive oropharyngeal carcinoma.
authors.affiliation: Department of Pathology, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA. chioseasi@upmc.edu.
authors.forename: Simion I
authors.initials: SI
authors.lastname: Chiosea
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
authors.forename: Vivian W Y
authors.initials: VW
authors.lastname: Lui
authors.forename: Brenda
authors.initials: B
authors.lastname: Diergaarde
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Maxwell
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.forename: Seungwon W
authors.initials: SW
authors.lastname: Kim
authors.forename: Alyssa
authors.initials: A
authors.lastname: Luvison
authors.forename: Megan
authors.initials: M
authors.lastname: Miller
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000821:virology*; D058534:Class I Phosphatidylinositol 3-Kinases; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000821:virology*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae; D030361:Papillomavirus Infections; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051059:PTEN Phosphohydrolase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)