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

BMC Cancer

Simion I Chiosea¹  Jennifer R Grandis²  Vivian W Y Lui²  Brenda Diergaarde²  Jessica H Maxwell²  Robert L Ferris²  Seungwon W Kim²  Alyssa Luvison¹  Megan Miller¹  Marina N Nikiforova¹ 

[1] Department of Pathology, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA

[2] Department of Otolaryngology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA

关键词: HPV;    PTEN;    HRAS;    PIK3CA;    Oropharyngeal squamous carcinoma;   

Others  :  859190
DOI  :  10.1186/1471-2407-13-602

 received in 2013-06-02, accepted in 2013-12-06,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Chiosea et al.; licensee BioMed Central Ltd.

【 图 表 】

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