PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous cell carcinoma

Simion I. Chiosea, Jennifer R. Grandis, Vivian W.Y. Lui, Brenda Diergaarde, Jessica H. Maxwell, Robert L. Ferris, Seungwon W. Kim, Alyssa Luvison, Megan Miller, Marina N. Nikiforova

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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. Methods and 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.

Original languageEnglish (US)
Article number602
JournalBMC Cancer
Volume13
DOIs
StatePublished - Dec 17 2013
Externally publishedYes

Keywords

  • HPV
  • HRAS
  • Oropharyngeal squamous carcinoma
  • PIK3CA
  • PTEN

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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