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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

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

Authors: 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

Published in: BMC Cancer | Issue 1/2013

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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.
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Metadata
Title
PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous cell carcinoma
Authors
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
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-602

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