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BMC Cancer. 2013 Dec 17;13:602. doi: 10.1186/1471-2407-13-602.

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

Author information

1
Department of Pathology, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA. chioseasi@upmc.edu.

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.

PMID:
24341335
PMCID:
PMC3878565
DOI:
10.1186/1471-2407-13-602
[Indexed for MEDLINE]
Free PMC Article

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